Electroencephalography and Clinical Neurophysiology , 1979, 47:515--523 515 © Elsevier/North-Holland Scientific Publishers, Ltd. FOVEAL VERSUS PERIPHERAL RETINAL RESPONSES: A NEW ANALYSIS FOR EARLY DIAGNOSIS OF MULTIPLE SCLEROSIS P.M. ROSSINI, M. PIRCHIO *, D. SOLLAZZO and C. CALTAGIRONE Clinic for Nervous and Mental Diseases, Catholic University, Rome and * Neurophysiology Laboratory, C.N.R., Pisa (Italy) (Accepted for publication: January 30, 1979) Estimates of the proportion of patients with acute optic neuritis later developing mul- tiple sclerosis (MS) vary from 11.5% (Kurland et al. 1963) to 85% (Lynn 1959; McAlpine 1964). Recently the necroscopic reports of Lumsden {1970) showed that the optic nerve represents one of the commonest sites for plaques in MS; this has been confirmed by the fundoscopic findings of Frisen and Hoyt (1974) suggesting the presence of focal and diffuse attrition of retinal axons in MS even in the absence of clinical involvement of visual function. By examining the peripapillary nerve fibre layer in 17 patients, Feinsod and Hoyt {1975) found two main patterns of fundal abnormality: (i) slit-like defects in the arcuate nerve fibres combined with diffuse thinning of the nerve fibre layer; (ii) diffuse thinning of temporal peripapillary bundles with a lesser degree of thinning in the remaining sectors surrounding the optic disc. A hidden visual loss has recently been emphasized by Regan et al. {1977) in 48 patients suffering from MS; this psychophys- ical study reports an altered contrast sensitiv- ity, mainly in the medium and high spatial frequency ranges {central vision). Other authors have shown that the average peak latencies of the occipital visual evoked potential (VEP) components elicited by flash or pattern reversal stimulation, are signif- icantly delayed in subjects with MS even in the absence of clinical damage in the visual pathways (Richey et al. 1971; Adachi-Usami et al. 1972; HaUiday et al. 1972; Namerow and Enns 1972; Feinsod et al. 1973; Halliday et al. 1973; Milner et al. 1974; Asselman et al. 1975; Feinsod and Hoyt 1975; Lehmann and Mir 1976; Lowitzsch et al. 1976; Paty et al. 1976; Regan et al. 1976; Chain et al. 1977). The VEPs recorded in response to bright flashes, however, vary as regards wave form and latency, from subject to subject. This variability makes it difficult to assess the abnormality of these responses and hence their clinical use in early diagnosis of MS is often unreliable. Many of the factors contributing to this variability are characteristics of the individual, influencing both the central and peripheral retinal responses. In order to reduce these fluctuations, in the present work, we attempted to compare the central and periph- eral responses and to analyse whether their difference in latency could present a less random variable in the clinical test for MS. According to our results, this latency difference between the responses obtained for central and peripheral stimulation (CPLD) allows an early definition of visual damage in many cases showing apparently normal values for both peripheral and central responses. Materials and Methods Patients and controls The VEP was studied in 85 patients with MS, 31 males {36%) and 54 females (64%), whose ages ranged from 18 to 57 years {aver-