Visual evoked potentials

Halliday et al. (1972) recorded visual evoked poten­ tials (VEPs) in 19 patients with unilateral optic neuritis, using two types of stimuli: a black and white chequerboard pattern-reversal and an unstructured flash. The responses to pattern-reversal stimulation were significantly delayed in 18 affected eyes and in two clinically unaffected ones. The mean VEP amplitude was reduced by half and the mean latency increased by about 30% when comparing symptomatic with asymptomatic eyes. No comparable increase in latency was found in the flash responses. These were greatly at­ tenuated in two patients only, who were in the acute stage of the attack and had a markedly reduced visual acuity. This abnormality, however, recovered quickly. Thus, flash stimulation was abandoned in following investigations be­ cause of its low sensitivity in detecting optic nerve pathology. In a subsequent paper, Halliday et al. (1973a) described the evolution of the VEP abnormalities following an attack of optic neuritis. In typical cases, the

amplitude decreased in coincidence with the drastic reduc­ tion of the visual acuity, while the latency of any

phase, the amplitude became larger with improvement of vi­ sion, often reaching virtually normal values, whereas the latency remained prolonged. Thus, there was a dissociation between VEP amplitude and latency and a response of in­

creased latency but preserved waveform was considered to be a typical sign of a previous attack of optic neuritis.

Subsequent studies aimed to assess the sensitivity of VEPs in revealing optic nerve pathology in MS. Halliday et al. (1973b) recorded delayed responses in 49/51 patients

(96%). Of these, 24 had a history of optic neuritis and 25 were visually asymptomatic. Eleven patients out of the 51 underwent examination of the fundi, colour vision and visual fields and in four of them a delayed VEP was the only sign of optic nerve pathology. In succeeding inves­ tigations, the incidence of VEP abnormalities in MS was lower than that reported by Halliday et al. (Asselman et al., 1975; Mastaglia et al., 1976; Matthews et al., 1977; Trojaborg and Petersen, 1979). The overall yield varied from 50% to 72% and increased with the certainty of diag­ nosis: 20% to 38% in possible, 33% to 83% in probable and 75% to 96% in definite MS cases. Abnormalities confirmed optic nerve disease in 83% to 100% of patients with history of optic neuritis and revealed clinically silent lesions in 47% to 70%. Asselman et al. (1975) recorded delayed

responses in 70% of eyes with normal or slightly impaired visual acuity and in 44% of those with normal or marginally

affected colour vision; overall, 28% of eyes with no symptoms or signs of optic nerve involvement had delayed VEPs.

VEP abnormalities were also reported in 46% (Asselman et al., 1975) or 50% (Hennerici et al., 1977) of patients with an isolated brainstem syndrome and in 25% (Asselman et al., 1975) or 10% (Blumhardt et al., 1982a) of patients with acute remitting spinal cord syndrome. Some studies

focused on the slowly progressive spastic paraparesis of the middle age, which shows no signs of involvement outside the spinal cord but has been found to develop spatial and temporal dissemination of neurological deficits in 20% of cases during a follow up period of five to 10 years

(Marshall, 1955). The incidence of abnormal VEPs in this condition showed a marked variability between studies: 5/22 cases (Asselman et al., 1975), 19/25 (Bynke et al., 1977) and 7/9 (Matthews et al., 1977). Blumhardt et al. (1982a) reported abnormal VEPs in 12/36 (33%) patients with chronic relapsing and in 23/64 (36%) cases with chronic progressive spastic paraparesis. The incidence showed a threefold in­ crease in recordings performed between three and six years from the onset of symptoms as compared with less than three years, suggesting that at this time in the course of the disease dissemination outside the spinal cord occurred.

After an episode of acute optic neuritis, the full- field VEPs may show some characteristic waveform altera­ tions, which are consistent with a more marked involvement

of the macular than paramacular fibres. One of these abnor­ malities is the so called "pseudo” delay (Halliday, 1982b).

In this situation, the response from the central part of the visual field, PlOO, is greatly reduced and masked by the potential arising from the peripheral part of the field. The latter terminates with a positivity peaking at about 135 ms (P135), which can sometimes be mistaken for a delayed PlOO. PlOO and P135 can be discriminated by

stimulating the left and right half-field. In hemifield responses, PlOO and P135 can be shown to project

predominantly to opposite sides of the scalp, the PlOO ip- silateral and the P135 contralateral to the stimulated half field (Blumhardt et al., 1978). Another morphological ab­ normality of the full-field VEP is a "w-shaped" waveform, which usually results from superimposition of the P135 on a partially attenuated PlOO (Blumhardt, 1987).

Recording of VEPs has been used to elucidate the mechanism of Uhthoff's symptom, which is a temporary im­ pairment of vision following physical exercise or a hot bath. Persson and Sachs (1980) studied seven MS patients with Uhthoff's symptom before and after exercise. The VEP

amplitude decreased in coincidence with reduction of the visual acuity and subsequently increased with improvement of vision. This suggested evidence that a reversible con­ duction block occurred during exercise.

In an attempt to ascertain whether VEPs are a useful technique for monitoring disease activity, Matthews and Small (1979) carried out serial recordings in two groups of patients with definite or probable MS for a) 18 and b) one to 40 months. In three patients of the former group, the VEP latency increased following a mild visual relapse and thereafter remained more prolonged than before. In the lat­ ter group, there was a reasonable correlation between

changes of the visual acuity and VEP latency. A deteriora­ tion or improvement of the visual acuity was accompanied by a prolongation or shortening of the VEP latency, respec­ tively, in 24/39 eyes (61%). In nine of these, the latency returned to normal values. The VEP was unchanged in 37/58 eyes (64%) in which the visual acuity was stable. Thus, there was a certain degree of correlation between visual and VEP changes occurring during the course of the disease.

Despite the fact that at autopsy plaques are often found in the postchiasmal pathways and especially in the optic radiations, in the literature there are few reports of VEP abnormalities consistent with retrochiasmal

demyelination. In the series published by Onofrj et al. (1982), concerning patients with homonymous hemianopic defects of different origin, two had MS. In these, on full and left or right half field stimulation the PlOO was at­ tenuated at scalp electrodes ipsilateral to the defective hemifield. In an MS patient with a right homonymous

PlOO to a full field stimulus in the channels ipsilateral to the defective hemifields, the abnormal response dis­ tribution being similar for both eyes. This type of dis­ tribution, characteristic of unilateral retro-chiasmal pathology, was called "uncrossed asymmetry". In another patient, who had no visual symptoms (Halliday, 1982c), the

left homonymous hemifield responses were significantly at­ tenuated as compared to the right homonymous hemifield com­ ponents. In a detailed examination of the visual fields, a desaturation to red colour was found in the left homonymous half-fields. In one investigation of 32 patients with le­ sions of the posterior visual pathways (Blumhardt et al., 1982b), VEPs were recorded in two MS patients within a few days of the onset of homonymous hemianopia. Responses from the affected hemifields were absent in one case and

markedly attenuated in the other.

It had been earlier on established that during the recovery phase of acute optic neuritis the amplitude of the VEP increases, paralleling the improvement of vision, while its latency remains prolonged (Halliday et al., 1973a, see above). Subsequent studies have shown that the VEP latency shortens during the weeks or months following the attack. The reported incidence of improvement is 32% during four weeks follow up (Diener and Scheibler, 1980), 26% during 14 weeks (De Weerd and Jonkman, 1982), 14% during 12 months

(Confraveux et al., 1982), 24% during 18 months (Matthews and Small, 1979) and 39% during 46 months (Hely et al..

1984). Full normalisation of the VEP latency has been reported in less than 10% of eyes, during a follow up period not exceeding 18 months (Matthews and Small, 1979; De Weerd and Jonkman, 1982). The improvement of the VEP latency after acute optic neuritis appears to be more con­ sistent in childhood (Kriss et al., 1988). Changes of the VEP amplitude are controversial: in one investigation a deterioration of this parameter was detected during 18 months follow-up (Matthews and Small, 1979), while in another no significant overall change was recorded during 14 to 28 months (Carroll et al., 1984). For a more detailed description of these studies see paragraph 5.2.1.

After the introduction of MRI in the investigation of MS, studies have been carried out to compare the sen­

sitivity of this technique with that of VEP recording in detecting demyelinating optic nerve lesions. In the report by Miller et al. (1988b) on 37 patients who had experienced an attack of acute optic neuritis, VEPs were abnormal in 100% of symptomatic and 27% of asymptomatic eyes, whereas MRI showed a optic nerve lesion in 84% of affected and 20% of unaffected optic nerves. This demonstrates that, using current imaging methods, VEP recording is more sensitive than MRI in revealing demyelinating optic nerve lesions