Clinical Evaluation of Eye Movements in Spinocerebellar Ataxias

Abstract

Background Ocular motor abnormalities reflect the varied neuropathology of spinocerebellar ataxias (SCAs) and may serve to clinically distinguish the different SCAs. We analyzed the various eye movement abnormalities detected prospectively at the baseline visit during a large multicenter natural history study of SCAs 1, 2, 3, and 6. Methods The data were prospectively collected from 12 centers in the United States in patients with SCAs 1, 2, 3, and 6, as part of the Clinical Research Consortium for Spinocerebellar Ataxias (NIH-CRC-SCA). Patient characteristics, ataxia rating scales, the Unified Huntington Disease Rating Scale functional examination, and clinical staging were used. Eye movement abnormalities including nystagmus, disorders of saccades and pursuit, and ophthalmoparesis were recorded, and factors influencing their occurrence were examined. Results A total of 301 patients participated in this study, including 52 patients with SCA 1, 64 with SCA 2, 117 with SCA 3, and 68 with SCA 6. Although no specific ocular motor abnormality was pathognomonic to any SCA, significant differences were noted in their occurrence among different disorders. SCA 6 was characterized by frequent occurrence of nystagmus and abnormal pursuit and rarity of slow saccades and ophthalmoparesis and SCA 2 by the frequent occurrence of slow saccades and infrequent nystagmus and dysmetric saccades. SCA 1 and SCA 3 subjects had a more even distribution of eye movement abnormalities. Conclusions Prospective data from a large cohort of patients with SCAs 1, 2, 3, and 6 provide statistical validation that the SCAs exhibit distinct eye movement abnormalities that are useful in identifying the genotypes. Many of the abnormalities correlate with greater disease severity measures.

The Initial Symptom and Motor Progression in Spinocerebellar Ataxias

“…SCA2 patients can have slow saccades, postural and action tremor, polyneuropathy, upper motor neuron signs, and parkinsonism, which could be a predominant feature in some cases. SCA2 cases with longer CAG repeats also often have myoclonus, dystonia, and myokymia [20, 21, 25]. SCA3 patients can have spasticity and oculomotor abnormality and SCA3 can be further divided into 5 subtypes.…”

Oculomotor deficits in spinocerebellar ataxia type 3: Potential biomarkers of preclinical detection and disease progression

“…Becauseofthefrequentinvolvementofthecerebellumandbrainstem, oculomotor disturbances, including square-wave jerk (SWJ), gaze-evoked nystagmus (GEN), impaired smooth pursuit eye movement (SPEM), and dysmetric saccade, are main characteristics of SCA3,someofwhichhavealsobeenrecognizedasdistinguishingfea-turesbetweenSCA3andotherSCAs. [5][6][7][8][9][10] Agrowingbodyofevidence indicatesthatthepreclinicalstageofSCAsisalreadycharacterizedby detectableoculomotorsigns,includingslowingofsaccadeinpreclini-calstageofSCA2andSCA7,saccadedysmetriainSCA6,andimpaired SPEMinSCA17. 2,11 Recently,GENwasfirstlyinvestigatedbyclinical observationinpreclinicalstageofSCA3(pre-SCA3).…”

Depression and clinical progression in spinocerebellar ataxias

“…In addition to adult-onset progressive cerebellar ataxia, other motor features such as pyramidal signs and eye movement disorders are also often associated with SCAs [3]. Pathological CAG repeat expansions are the major genetic underpinning and the encoded polyglutamine aggregates are found in neurons of SCA brains [4].…”