Ataxia

Ataxia, defined as incoordination of voluntary muscle movement, is a neurological sign, not a disease. It can be the chief complaint or part of the presenting symptoms, and it is usually caused by cerebellar dysfunction, impaired vestibular or proprioceptive afferent input to the cerebellum.  

Patients with ataxia usually present with poor coordination of stance and gait, difficulty with fine motor tasks, impaired swallowing and speech, and various abnormalities of eye movements. 

Ataxia can start at any age, from childhood to old age and can be caused by multiple diseases, from untreatable genetic causes to treatable infection, and including chronic diseases such asmultiple sclerosis, cancer or vitamin deficiency. It can start acutely or progress slowly (1,2).   

Neurophysiological assessments are often equated with electrophysiological assessments, that is, nerve conduction studies, electromyography (EMG), sensory and motor evoked potentials (SEP, MEP), and electroencephalography (EEG). These are routine procedures and are widely available in neurology departments. Electrophysiological methods are useful to detect extracerebellar involvement, but none of these measures allow demonstration or quantification of cerebellar involvement, the core problem in most types of ataxias. Cerebellar brain inhibition (CBI) can be assessed by transcranial magnetic stimulation, but it has not been systematically applied in ataxias and is not part of the diagnostic routine. Some oculomotor abnormalities are highly specific to cerebellar dysfunction, making their analysis a valuable aid in diagnosing cerebellar ataxia syndromes and representing potential diagnostic biomarker (3,4). BulbiCAM® provides clinicians with an objective reliable tool to assess cerebellar oculomotor functions and help improve diagnosis through validated diagnostic biomarkers (5). 

The cerebellum plays a major role in the control of eye movements and in the evaluation of a patient with cerebellar dysfunction. Recognizing the pattern of ocular motor and/or vestibular impairment is often a key step toward the correct diagnosis. Patients with cerebellar ataxia often exhibit oculomotor deficits such as ocular instability (nystagmus and saccadic intrusions), abnormalities in slow eye movements (impaired smooth pursuit and vestibulo-ocular reflex), deficits in saccades, ocular misalignment (skew deviation and strabismus) (4). Despite their high prevalence, oculomotor deficits evaluation is disproportionally neglected in clinical ataxia scales such as the Brief Ataxia Rating Scale (BARS), the International Cooperative Ataxia Rating Scale (ICARS) and the Scale for the Assessment and Rating of Ataxia (SARA) (6–8). Although the Scale for Ocular Motor Disorders in Ataxia (SODA) (9) specifically addresses these abnormalities, its application remains limited by subjectivity. Eye movements can now be recorded by increasingly available and easy to use non-invasive eye-tracking technologies offering the advantage to be able to reveal small-amplitude eye movements that cannot be seen with the naked eye, allow the accurate description and quantification of eye movement metrics and dynamics such as latency, accuracy, or peak saccade velocity, reveal abnormal eye movement patterns such as complex, unusual, or uncommon ocular oscillations, investigate in detail gaze fixation. 

Spinocerebellar ataxias (SCAs) are inherited from progressive neurodegenerative disorders and belong to the heterogeneous group of cerebellar ataxias. In addition to cerebellar dysfunction, some SCAs involve other systems, such as brainstem, as well as ocular structures, including the retina and optic nerve. Because the clinical presentation is extremely heterogeneous, combinations of several clinical symptoms can help distinguish between different SCAs types and aid in differential diagnosis (10,11).  In addition, visual disturbances may precede other symptoms in certain types of SCAs, underscoring the importance of their careful evaluation and close monitoring (10,12). From an ophthalmological prognostic standpoint, it is an important issue that a diverse range of ophthalmic abnormalities, especially the optic nerve and retina, and eye movement abnormalities have been reported in patients with SCAs. Considerable visual impairment can occur in the affected individuals resulting from these abnormalities. (10), reinforcing the importance of careful evaluation and monitoring. Both eye movements and ophthalmic parameters can be measured with BulbiCAM® for a global assessment. 

Being able to provide both an accurate and early diagnosis is critical for clinical trials and may prompt the pursuit of disease-modifying treatments. Quantitative oculomotor parameters havebeen suggested as potential endpoints in Ataxia studies and may provide sufficient effect sizes even in small cohorts of rare diseases while maintaining low variability (9,13). Oculomotor abnormalities have been shown to correlate with disease severity and duration, imaging measures of atrophy and treatment effect (12,14),15) making eye-tracking a valuable tool to evaluate and follow-up patients.  

Oculomotor assessment could play a key role in cerebellar ataxia, assisting both clinicians and researchers at every stage of the disease, from diagnosis to the evaluation of impairment.