Vestibular and Saccadic Abnormalities in Gaucher’s Disease

Abstract

Gaucher's disease (GD) is a hereditary lysosomal storage disease characterized by abnormal deposition of glucocerebroside due to the enzyme glucocerebrosidase deficiency, resulting in multi-organ pathology. GD type III has a progressive neurological involvement. We studied the vestibular and saccadic abnormalities in GD type III to determine if these parameters may be useful for assessing neurological involvement. We evaluated the vestibular and saccadic responses of two siblings with genetically identified GD type III on enzyme replacement therapy. Vestibular functions were assessed with the head impulse test (HIT), vestibular evoked myogenic potentials (VEMPs), and electrical vestibular stimulation (EVS). Saccadic functions were investigated with volitional horizontal and vertical saccades to AE20. Three-dimensional head and eye movements were recorded with dual-search coils and VEMP with surface electrodes. HIT showed impaired individual semicircular canal function with halved angular vestibuloocular reflex (VOR) gains and absent horizontal refixation saccade. Ocular and cervical VEMPs to air-conducted clicks were absent in the older sibling, and only cervical VEMP was present in the younger sibling indicating otolithic dysfunction. EVS showed prolonged onset latency and attenuated tonic and phasic responses suggesting impaired neural conduction and vestibular function. Horizontal saccadic velocity was miniscule (<30 /s) and multiple back-to-back saccades with saccade-vergence interaction were utilized to minimize eye position error in the older sibling. Vertical saccades were slightly abnormal, but vergence and smooth pursuit were normal in both siblings. Our findings suggest that GD affected the vestibular nuclei in addition to the paramedian pontine reticular formation. These vestibular and saccadic abnormalities may be useful biomarkers to monitor neurological deterioration.

Oculomotor and Vestibular Findings in Gaucher Disease Type 3 and Their Correlation with Neurological Findings

“…As horizontal and later vertical saccades are highly impaired early in the course of the disease, they were used as a primary endpoint to investigate treatment with miglustat ( 5 ). A study of two siblings with GD3 suggested that the vestibulo-ocular reflex (VOR) might also be impaired in GD3 patients ( 6 ). Although saccadic eye movement abnormalities have been described, a comprehensive study of all forms of eye movements in GD3, including pursuit and vestibular-related movements in a large cohort of GD3 patients, has not been published yet.…”

Bilateral Vestibular Dysfunction

“…44 Otherwise, BVD may be observed in spinocerebellar ataxia (SCA) types 1, 2, 3, and 6, episodic ataxia type 2, Friedreich's ataxia, Gaucher's disease, and Cronkhite-Canada's syndrome. 3,4,[45][46][47][48][49] Of note, bilateral deafness is usually associated with BVD in Friedreich's ataxia. 50 In patients with advanced SCA type 6, a pure cerebellar form of SCA, the bilaterally positive HITs are probably because of the floccular involvement.…”

Video Head Impulse Testing: From Bench to Bedside

“…85 Global loss of SCC function can cause confusion with BV, but the paucity or slowing of catch-up saccades provides the diagnostic clue. 86 Vestibular deficits in Gaucher's disease likely reflects neuronal loss in the abducens and vestibular nuclei. 87 Eye movement and vHIT abnormalities have been shown to correlate with clinical rating scales, representing promising biomarkers for future clinical trials.…”