The saccadic and neurological deficits in type 3 Gaucher disease.

William Benko,Roscoe O Brady,Edythe A Wiggs,Markus Ries,Edmond J Fitzgibbon,Raphael Schiffmann,Andreas Meisel

doi:10.1371/journal.pone.0022410

Abstract

Our objective was to characterize the saccadic eye movements in patients with type 3 Gaucher disease (chronic neuronopathic) in relationship to neurological and neurophysiological abnormalities. For approximately 4 years, we prospectively followed a cohort of 15 patients with Gaucher type 3, ages 8–28 years, by measuring saccadic eye movements using the scleral search coil method. We found that patients with type 3 Gaucher disease had a significantly higher regression slope of duration vs amplitude and peak duration vs amplitude compared to healthy controls for both horizontal and vertical saccades. Saccadic latency was significantly increased for horizontal saccades only. Downward saccades were more affected than upward saccades. Saccade abnormalities increased over time in some patients reflecting the slowly progressive nature of the disease. Phase plane plots showed individually characteristic patterns of abnormal saccade trajectories. Oculo-manual dexterity scores on the Purdue Pegboard test were low in virtually all patients, even in those with normal cognitive function. Vertical saccade peak duration vs amplitude slope significantly correlated with IQ and with the performance on the Purdue Pegboard but not with the brainstem and somatosensory evoked potentials. We conclude that, in patients with Gaucher disease type 3, saccadic eye movements and oculo-manual dexterity are representative neurological functions for longitudinal studies and can probably be used as endpoints for therapeutic clinical trials.Trial RegistrationClinicalTrials.gov NCT00001289

Highlights

Gaucher disease is an autosomal recessive disorder that results from the deficiency of the lysosomal enzyme glucocerebrosidase and the accumulation of glucosylceramide in macrophages systemically in most patients [1]
In order to fully characterize the saccadic abnormalities in Gaucher disease, we prospectively studied the saccadic characteristics in 15 patients with GD3, with an emphasis on vertical saccades, using a reliable recording method for eye movements
The brainstem areas attributed to saccadic control include the parapontine reticular formation (PPRF) for horizontal saccades and the midbrain rostral interstitial nucleus of the medial longitudinal fasciculus for vertical saccades [10]

Summary

Introduction

Gaucher disease is an autosomal recessive disorder that results from the deficiency of the lysosomal enzyme glucocerebrosidase and the accumulation of glucosylceramide in macrophages systemically in most patients [1]. The chronic neuronopathic form of Gaucher disease (type 3 Gaucher disease, GD3), is a neurological disorder that has a very variable clinical expression. It is associated with an accumulation of glucosylceramide in perivascular macrophages and in brain glial cells and in neurons [2,3]. The hallmark clinical abnormality of patients with neuronopathic Gaucher disease consists of markedly slow horizontal saccades [3,5]. We and others have observed for some time that vertical saccades are slow as well but to a lesser extent and this deficit lags in time [6,7,8]

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Conclusion