Saccades in adult Niemann-Pick disease type C reflect frontal, brainstem, and biochemical deficits

Background: The autosomal recessive disorder Niemannn-Pick type C (NPC) presents in adulthood with psychosis or cognitive deficits associated with supranuclear gaze palsies. While saccadic innervation to the extraocular muscles is generated in the brainstem, the frontal lobes play an integral role in the initiation of volitional saccades and the suppression of unwanted reflexive saccades. No study has examined the frontally driven volitional control of saccadic eye movements in NPC. Objective: To examine self-paced and antisaccades as well as reflexive saccades in adult patients with NPC, a disorder known to affect brainstem and frontal cortical function. Methods: Three biochemically confirmed adult patients with NPC were compared with 10 matched controls on horizontal saccadic and antisaccadic measures using an infrared limbus eye tracker. Patients' cholesterol esterification and filipin staining, Mini-Mental State performance, and NPC symptom level were rated. Results: Reflexive saccade latency ranged from shorter to longer than normal, reflexive saccade gain was reduced, asymptotic peak velocity was reduced, fewer self-paced saccades were generated, and increased errors on antisaccades were made by patients compared to controls. Patients with more severe biochemical, cognitive, and symptom deficits performed most poorly on brainstem and frontal ocular motor measures. Paradoxically, less severe illness was associated with an abnormally reduced saccadic latency. Conclusions: Ocular motor measures provide an index of disease severity in Niemannn-Pick type C (NPC) and may be a useful adjunct for monitoring the illness progress and medication response. Reduced saccadic latency may result from inadequate fixation input from abnormally functioning frontal eye fields in NPC. Neurology (R) 2009; 72: 1083-1086