An ERG and OCT study of neuronal ceroid lipofuscinosis CLN2 Battens retinopathy

Abstract

Background Late infantile neuronal ceroid lipofuscinosis (CLN2 Batten disease) is a rare, progressive neurodegenerative disease of childhood. The natural history of motor and language regression is used to monitor the efficacy of CNS treatments. Less is known about CLN2 retinopathy. Our aim is to elaborate the nature, age of onset, and symmetry of CLN2 retinopathy using visual electrophysiology and ophthalmic imaging. Subjects and methods We reviewed 22 patients with genetically confirmed CLN2 disease; seventeen showing classical and five atypical disease. Flash electroretinograms (ERGs), flash and pattern reversal visual evoked potentials (VEPs), recorded from awake children were collated. Available fundus images were graded, optical coherence tomography (OCT) central subfoveal thickness (CST) measured, and genotype, age, clinical vision assessment and motor language grades assembled. Results ERGs show cone/rod system dysfunction preceded by localised macular ellipsoid zone disruption on OCT from 4.8 years. Electroencephalogram (EEG) time-locked spikes confounded both pattern 6/17 (35%) and flash VEPs 12/16 (75%). Paired right eye (RE) and left eye (LE) ERG amplitudes did not differ significantly for each flash stimulus at the p 0.001 level, Wilcoxon ranked signed test. Cone ERGs show a functional deficit before CST thinning in classical disease. Optomap hyper fundus autofluorescence (FAF) at the fovea was noted in three patients with normal ERGs. The oldest patient showed an ovoid aggregate above the external limiting membrane at the fovea, which did not affect the PERG. Conclusion ERG findings in CLN2 retinopathy show symmetrical cone-rod dysfunction, from 4y10m in this series, but a broad range of ages when ERG function is preserved.

Neurophysiological Findings in Neuronal Ceroid Lipofuscinoses

“…Abnormal VEPs have been found in about 75% of patients with CLN2 at a median age of 4.5 years (25). Furthermore, a more recent study on patients with CLN2 evidenced that most patients (89%) had an early and high-amplitude pattern reversal in VEPs, whereas few patients showed a bifid waveform, which is associated with a central scotoma, indicative of maculopathy or macular pathway dysfunction such as optic atrophy (47).…”

“…The pattern-reversal VEP waveform is preferred to the flash VEP waveform, which shows a wide inter-individual variability. On the contrary, the pattern-reversal VEP has a relatively constant single positive peak throughout life and is a strong index of macular pathway function (47).…”

“…Variability of results may be due to the retrospective nature of the studies and the different ages and phases of the disease in which visual tests have been performed (25,41,47).…”

“…ERG is currently used to characterize the physiological changes in the degenerating retina in patients affected by NCLs. It allows to identify the retinopathy, which consists of symmetrical cone-rod dystrophy (47,50).…”

“…In patients with CLN2, it has been demonstrated that changes in ERG appear even before the macular disruption on optical coherence tomography (OCT) from the age of 4 years and 10 months (47). Abnormal ERG has been reported in 66% of patients at a median age of 4.5 years (25).…”