Oculomotor abnormalities in children with Niemann-Pick type C

Abstract

Niemann-Pick type C (NP-C) is a rare recessive disorder associated with progressive supranuclear gaze palsy. Degeneration occurs initially for vertical saccades and later for horizontal saccades. There are studies of oculomotor degeneration in adult NP-C patients [1, 2] but no comparable studies in children. We used high-resolution video-based eye tracking to record monocular vertical and horizontal eye movements in 2 neurological NP-C patients (children with clinically observable oculomotor abnormalities) and 3 pre-neurological NP-C patients (children without clinically observable oculomotor abnormalities). Saccade onset latency, saccade peak velocity and saccade curvature were compared to healthy controls (N=77). NP-C patients had selective impairments of vertical saccade peak velocity and vertical saccade curvature, with slower peak velocities and greater curvature. Changes were more pronounced in neurological than pre-neurological patients, showing that these measures are sensitive to disease progress, but abnormal curvature and slowed downward saccades were present in both groups, showing that eye-tracking can register disease-related changes before these are evident in a clinical exam. Both slowing, curvature and the detailed characteristics of the curvature we observed are predicted by the detailed characteristics of RIMLF population codes. Onset latencies were not different from healthy controls. High-resolution video-based eye tracking is a promising sensitive and objective method to measure NP-C disease severity and neurological onset. It may also help evaluate responses to therapeutic interventions.

Dopamine promotes instrumental motivation, but reduces reward-related vigour

“…A saccade’s velocity is tightly governed by its amplitude, a relation known as the ‘main sequence’ ( Bahill et al, 1975 ). To account for this, we regressed out the effect of amplitude on peak velocity leaving peak saccade velocity residuals as our main measure of response vigour (see Figure 1e ), as in previous work ( Blundell et al, 2018 ; Manohar et al, 2017 ; Muhammed et al, 2020 ; Muhammed et al, 2016 ; Van Opstal et al, 1990 ). This measures how much faster each saccade is than the speed predicted from its amplitude.…”

“…This was done for each participant’s separate session. This approach has been used before, by us and others ( Blundell et al, 2018 ; Manohar et al, 2017 ; Muhammed et al, 2020 ; Muhammed et al, 2016 ; Van Opstal et al, 1990 ), and it is similar to simply including amplitude as a covariate when analysing raw peak velocity, but it does not reduce the degrees of freedom and yields simpler to interpret results. Moreover since motivation increases amplitude ( Manohar et al, 2019 ), including amplitude as a covariate would mean that amplitude would compete with motivation to explain variance in velocity, potentially resulting in overestimation of motivation effects.…”

Eye involvement in inherited metabolic disorders

“…Extraocular manifestations are expected including dysmorphic features, protein-losing enteropathy, pericardial effusions. 15 Early-onset mitochondrial disorders including those presenting with Leigh and Leigh-like syndrome can present with new-onset squint together with other loss of previously acquired skills often after a minor febrile illness; imaging studies together with biochemical testing are the first steps in the diagnostic workup. Mitochondrial disorders can also present later in life with primary ocular motor defects, including progressive external ophthalmoplegia as either an isolated feature, or as part of a multisystem mitochondrial defect such as Kearn Sayre Syndrome.…”

“…Extraocular manifestations are expected including dysmorphic features, protein-losing enteropathy, pericardial effusions. 15…”

Niemann-Pick Disease Type C with Isolated Splenomegaly: A Case Report in a Child

“…In Brazil, its incidence and prevalence remain unknown. [1][2][3][4][5] NPC has a broad spectrum of clinical phenotypes ranging from a rapidly progressive and fatal disorder in the neonatal period to chronic neurodegenerative disease in adulthood. Thus, the age of onset of the disease can be used to facilitate the classification of NPC.…”