Visual evoked potentials in ON-pathway disorders

Great Ormond Street Hospital, London, UK; 2 Stem Cells and Regenerative Medicine Section, UCL Institute of Child Health, London, UK; 3 Dubowitz Neuromuscular Centre, UCL Institute of Child Health and Great Ormond St, London, UK; 4 Department of Metabolic Medicine, Great Ormond Street Hospital for Children, London, UK Purpose: Some animal models of ON-pathway dysfunction are reported to show disorganised ganglion cell firing rates. The purpose of this study is to examine whether patients manifesting ERG evidence of ON-pathway dysfunction—associated with conditions such as Duchenne Muscular Dystrophy (DMD), congenital disorders of glycosylation (PMM2-CDG), or Congenital Stationary Night Blindness (CSNB)—show evidence of altered VEPs, which may indirectly reflect ganglion cell firing. Methods: Pattern reversal VEPs (pVEPs) from patients identified with ‘negative’ ERGs were analysed. The amplitude and latency of pVEPs elicited to checks of 50’ side length, which phase reversed 3/s in a field subtending 30 degrees viewed at 1 m recorded from Oz referred to Fz were collated. These were compared with normative data. The study group comprised patients with DMD (n = 15, seven with mutations pre exon 30 and eight with post exon 30), PMM2-CDG (n = 10) and CSNB (n = 32). The CSNB cohort was further subdivided into 19 individuals with incomplete CSNB (iCSNB) and 13 with complete CSNB (cCSNB), of whom seven were female and six male. Results: The normative range of pVEP latency for a 50’ check size in the age range of 8–15 years is 90–116 ms. The following patient groups fell within normal range: (1) All DMD patients had clinically normal pVEP latencies (median 98 ms, range 92–114 ms). The groups were stratified according to mutation position, before exon 30 (median 100 ms, range 92–114 ms) and after exon 30 (median 98 ms, range 95–107 ms). None of these patients showed nystagmus. (2) All PMM2-CDG patients had normal pVEP latencies (median 107 ms, range 95–115 ms), except for one patient with a nondetectable response to 50’checks. Four of these patients had nystagmus. (3) All males with cCSNB had pVEP latencies just around normal range (median 112 ms, range 101–118 ms). One patient had nystagmus. Abnormal pVEPs were noted in three out of seven female cCSNB patients; two of these patients had nystagmus. Additionally, two of the three patients with abnormal pVEP had mutations in GRM6. Mutational analysis is pending on the third patient. The overall group pVEP median latency was 112 ms (range 103–131 ms). A majority of patients with iCSNB (16/19) showed abnormal pVEPs. Most showed delayed latencies (10/16), including four patients who did not have nystagmus. One patient had an abnormally small amplitude pVEP with normal latency. The remaining five patients had no detectable response to 50’ checks. None of the three iCSNB patients with normal pVEPs had nystagmus. The median latency of iCSNB patients with measurable responses was 121 ms (range 103–133 ms). Conclusions: In summary, we found patients with ONpathway disorders who manifested abnormalities in pVEP latency and amplitude consistent with altered ganglion cell firing. These abnormalities occurred in the absence of nystagmus in males with iCSNB and females with cCSNB. Funding: The Ulverscroft Foundation National Institute of Health Research Biomedical Research Centres, Great Ormond Street Hospital and University College London Institute of Child Health.