Visual evoked responses and visual symptoms in multiple sclerosis

Absolute latency, interocular difference in latency, and waveform of visual evoked responses (VER) to checkerboard reversal stimuli recorded from the midline of the skull were studied in 104 multiple sclerosis patients, 25 to 50 years of age, classified according to visual symptomatology. Group 1 had strong evidence of past or present optic neuritis. Patients with blurring of vision, diplopia, and undefined visual complaints were assigned to group 2, while group 3 contained patients with no visual symptoms but suspected diagnosis of multiple sclerosis on other grounds. The three parameters explored showed consistent association with the degree of visual involvement, as assessed by clinical impression, but their discriminatory power was diverse. Absolute latency was significantly longer in group 1 patients compared with groups 2 and 3, but it did not discriminate between the last two, whereas interocular difference in latency proved to be sensitive to differences between symptomatic (diplopia, blurring) and asymptomatic groups (2 and 3). Waveshapes were grouped into three categories based upon degree of distortion of the major positive peak, and their relative distribution among the three patient groups was found to be associated with symptomatology. We suggest that, in the production of symptoms such as diplopia, a temporal disparity of afferent impulses might be involved in much the same way that spatial incongruities between both eyes lead to impaired function. In this regard, interocular difference in latency rather than absolute latency would be a more accurate predictor of symptom development. The analysis of VER waveshape suggests, in addition, the importance of inhomogeneous involvement of the visual pathways in the production of symptoms during the evolution of multiple sclerosis.     

Pattern and flash visual evoked responses in multiple sclerosis

Summary In multiple sclerosis (MS), increase of delay may be important, but the earlier change is the behavior of the wave shape; amplitude is always lower even in MS patients without visual subjective symptomatology, provided not only flash but also pattern stimulation is performed. Normal amplitude with pattern stimulation does not necessarily mean normal with flash. Combining both stimulation methods, we obtained lowering of amplitude and change of wave shape in 100% of cases while latency was increased in only 77% of cases.Sectorial ischemic neuropathy, and open angle glaucoma patients show the same findings, which emphasizes that the method is not specific for demyelinating diseases, nor selective for papillomacular bundle involvement, but that VER, considering only its first components, reflects axonal damage somewhere in the visual pathway. Flash and pattern VER might be even more pathognomonic in MS than oligoclonal gammaglobulin fractionation on agar, positive in 75% of cases. It is suggested that subclinical MS cases should be submitted to full electro-ophthalmographic investigation.Paper presented at the Second Congress of the International Society of Neuro-ophthalmology, held 1 May 1978, at Airlee, VA, USA     

Practical application of patterned visual evoked responses in multiple sclerosis

Pattern reversal visual evoked potentials (VEP) were studied in a control group of 72 subjects and in 60 patients with multiple sclerosis. The recording system consisted of a visual stimulator for pattern production on a commercial TV connected to an EMG machine for displaying and averaging of the response. The normal values of latency, the upper limit of normality and right-left eye differences in our control group were compared with those given by different authors. Likewise a comparison of the positive VEP results in MS was carried out. The reasons for the variability of results were briefly discussed and the importance of control studies for each laboratory starting VEP recording was stressed. This test can easily be carried out in every clinical neurophysiological laboratory and it provides an excellent and rapid technique for the investigation of patients with suspected multiple sclerosis.     

Measuring evoked responses in multiple sclerosis.

Evoked potentials (EPs) have been widely utilised in Multiple Sclerosis (MS) patients to demonstrate the involvement of sensory and motor pathways. Their diagnostic value is based on the ability to reveal clinically silent lesions and to objectivate the central nervous system damage in patients who complain frequently of vague and indefinite disturbances which frequently occurs in the early phases of the disease. The advent of magnetic resonance imaging (MRI) techniques has greatly reduced the clinical utilisation of EPs, which is not fully justifiable, as the information provided by EPs are quite different from those provided by MRI. The abnormalities of evoked responses reflect the global damage of the evoked nervous pathway and are significantly correlated with the clinical findings, while the vast majority of MRI lesions are not associated to symptoms and signs. Transversal and longitudinal studies have demonstrated that EP changes in MS are more strictly related to disability than MRI lesion burden. On the contrary, MRI is more sensitive than EPs in revealing the disease activity. Evoked responses modifications observed in MS are not disease-specific; moreover longitudinal studies showed latency and morphology changes of evoked responses not always related to clinical changes. Such a dissociation can be explained both by technical factors and by subclinical disease activity. To reduce the negative impact of technical aspects, only reproducible parameters of the evoked responses should be used to monitor disease evolution and therapeutic interventions.     

Visually evoked responses in multiple sclerosis

Visually evoked cerebral responses (VERs) from the occipital and central areas were compared between 50 patients with multiple sclerosis and 50 control subjects. The average peak latencies of four occipital components (OII-OV) and two central ones (CIV and CV) were significantly delayed. In no instance was the amplitude significantly different. Routine EEGs were either entirely normal (16) or showed only minor findings (10) in 26 patients. Of this group, nine showed abnormal VERs. Seventeen patients had clinical symptoms or signs which pointed to spinal cord involvement only; nonetheless, eight in this group had abnormal responses. Inasmuch as changes in visually evoked potentials are not directly dependent upon the presence of a demonstrable field defect, the technique may be useful in detecting otherwise occult cerebral lesions.     

Pattern-onset visual evoked potentials in suspected multiple sclerosis.

Visual evoked potentials (VEPs) were obtained by monocular stimulation using a checkerboard pattern-reversal and pattern-onset technique. In 11 normal subjects, pattern-onset VEPs were generally larger, better defined, and less ambiguous than those elicited by pattern-reversal, because of the biphasic waveform characteristically obtained with pattern-onset stimulation. In 68 of 105 patients with possible multiple sclerosis, VEPs were normal in latency by both methods, and in nine adequate comparison was not possible. The incidence of normal VEPs to pattern-reversal was similar to that found in several other studies of patients with possible multiple sclerosis. Among the remaining 28 patients in whom VEP abnormalities were found, an increased latency was detected in 75% with the pattern-reversal technique, and in 96% by pattern-onset. In these patients, VEP abnormalities were obtained by monocular stimulation of each of 46 eyes, and among these the pattern-reversal technique yielded abnormalities in 59% and the pattern-onset method in 98%. These results indicate that VEPs elicited by pattern-onset are useful in investigating patients with suspected multiple sclerosis, and the diagnostic yield may be greater than with conventional pattern-reversal techniques.     

Pattern visual evoked potential luminance and multiple sclerosis.

Pattern visual evoked potentials (PVEPs) were recorded from 111 patients classified as having possible, probable or definite multiple sclerosis. Patients were stimulated with a checkerboard pattern using high and low luminances in order to test the hypothesis that an attenuated pattern luminance increases the detection rate of PVEP abnormalities. With increasing certainty of diagnosis, there was a concomitant increase in the incidence of PVEP abnormalities. However, there was no evidence that stimulating with a lower luminance pattern enhanced the sensitivity of the test. The same findings were also apparent when the patient data was analyzed according to the presence or absence of a history of optic neuritis or other visual symptoms. It is concluded that, within the luminance limits used in this study, the role of varied luminance in detecting demyelinating lesions in the optic nerves using the PVEP is minimal, although there was some limited evidence that a high level of luminance may be more appropriate than a low level.     

Reduced visual evoked responses in multiple sclerosis patients with optic neuritis: comparison of functional magnetic resonance imaging and visual evoked potentials.

The limited application of functional magnetic resonance imaging (fMRI) for investigations of multiple sclerosis (MS) patients has already shown that deficits of the motor, cognitive and visual systems may be identified by differences in the patterns of activation in response to a suitable stimulus. In MS patients with unilateral optic neuritis, the area of activation in the primary visual cortex, measured by fMRI techniques, is dramatically reduced in response to stimulation of the affected eye. The latency of the major positive component of the visual evoked potential (VEP) recorded upon stimulation of the affected eye is significantly increased in these patients, as compared to the unaffected eye and normal volunteers. We have found a correlation between the neural response measured using fMRI and the latency of the VEP. fMRI signal responses have the potential to provide more detailed topographic information relating to functional deficits in MS.     

Variability of cortically evoked motor responses in multiple sclerosis.

The calculated central motor conduction time (CMCT), onset latency variability (expressed as the mean consecutive difference; MCD) and amplitude (expressed as percentage of maximum peripheral M wave size) of electromyographic (EMG) responses in the first dorsal interosseous (FDI) muscle following magnetic motor cortex stimulation were investigated in 20 normal subjects and 21 patients with multiple sclerosis (MS). EMG responses were present in all patients studied. CMCT was prolonged (greater than 8.1 msec; the mean CMCT for normals plus 3 S.D.) in 19 out of 42 muscles (12 patients). Onset latency variability was increased (greater than 1.1 msec; mean plus 3 S.D. for normals) in 20 out of 42 muscles (14 patients). Maximal response amplitudes varied between 5% and 67% and were not significantly different from the normal group (range 16-64%). In 3 patients, increased onset latency variability was the only neurophysiological abnormality. Prolonged CMCT was the sole abnormal finding in only 1 patient. Abnormally large onset latency variability was associated with the clinical finding of both impaired fine finger movements and increased finger jerks. Abnormal CMCT was associated with increased finger jerks only. This study confirms the findings of prolonged CMCT in multiple sclerosis. The additional finding of abnormal variability in response latencies which correlates with the clinical signs suggests that this variability may also be a useful measure of pyramidal tract function.     

Visual evoked responses in patients with multiple sclerosis

The visual evoked response (VER) was evaluated in a series of multiple sclerosis patients and normal subjects. The data showed significant delays in wave peak latencies among the patient evoked responses. The prolonged latencies correlated closely with visual impairment; however, even patients with a previous history of visual impairment, but with no deficits noticeable on examination at the time of study, showed a delay in wave peak latencies. The results further suggest that the VER is primarily altered when there are central field defects.     

Brainstem impairment in multiple sclerosis: an assessment by multimodal evoked potentials

The usefulness of multimodal evoked potentials for the diagnosis of Multiple Sclerosis (MS) is established. Our purpose was to try a set of 3 EPs (BAEP, median SEP and trigeminal SEP) in the evaluation of brainstem dysfunction. 53 definite and probable MS patients have been examined; they were allotted to 3 groups according to the duration of the disease. Our results showed that median SEP is the most sensitive investigation, while BAEP and trigeminal SEP were abnormal in a smaller number of cases. The combined use of median and trigeminal SEPs supplied sufficient information on brainstem function, without using the complete set of EPs. No significant relation between EP abnormalities and duration of the disease was found.

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Sommario Scopo della nostra ricerca è la valutazione dell'efficacia di una batteria di Potenziali Evocati (BAEP, PES mediano e PES trigeminale) nell'evidenziare alterazioni del troncoencefalo nel corso di Sclerosi Multipla. Abbiamo esaminato 53 pazienti con SM definita o probabile, suddivisi in tre gruppi in base alla durata di malattia (<2 anni, >2<10 anni, >10 anni). I nostri risultati mostrano che il PES mediano risulta la metodica più sensibile, mentre il BAEP ed il PES trigeminale sono anormali in un minor numero di casi. L'uso combinato dei PES mediano e trigeminale consente di ottenere buone informazioni sulla funzione troncoencefalica senza dover ricorrere necessariamente alla intera batteria di esami. Non è stata riscontrata alcuna correlazione significativa tra anomalie dei Potenziali Evocati e durata di malattia.

     

Crossed acoustic response combined with visual and somatosensory evoked responses in the diagnosis of multiple sclerosis.

The crossed acoustic response, (CAR), a recently introduced test of brainstem function, has been studied in 66 patients with multiple sclerosis and 53 control subjects, and compared with conventional visual and somatosensory evoked responses (VER, SER). A latency abnormality was found in the CAR in 73% of patients, in the VER in 63%, and in the SER in 37%. Abnormalities have been related to the presence or absence of clinically detectable signs. All three responses detected subclinical lesions by showing abnormality in a proportion of multiple sclerosis patients who had no corresponding abnormal clinical signs (CAR 69%, VER 42%, SER 29%). The best diagnostic combination of responses was VER and CAR. Ninety per cent of patients had at least one of these two responses abnormal.     

Serial pattern shift visual evoked potentials in multiple sclerosis

Forty patients with MS initially tested in our laboratory were recalled for repeat PSVEP testing approximately two years later. Twelve normal controls were tested in a similar manner approximately two years apart. The PSVEP positive peak latency changed little in the 24 control eyes (mean 1.4 msec, range 0-6) over the study interval. Most MS patient eyes also showed little change in PSVEP latency over the two year study interval. Fifty-eight eyes changed 8 msec or less. Eighteen eyes showed a PSVEP latency increase of 10 msec or more. Six of these eighteen eyes were symptomatic (attack of clinical optic neuritis), twelve asymptomatic during the study interval. Symptomatic eyes tended to have greater latency increases during the study interval than asymptomatic eyes. Significant latency increases occurred with equal frequency in previously normal eyes (normal PSVEP on first test) and abnormal eyes (abnormal PSVEP on first test or previous clinical optic neuritis). Significant latency increases occurred with greater frequency in patients with a mixed or progressive course than in patients with a remitting-relapsing course, and in patients with greater disability rating (Kurtzke 3-7) than in patients with lower disability ratings (Kurtzke 0-2). Bilateral latency increases occurred during the study interval more frequently than expected by chance. Patient age and disease duration did not significantly influence the number of PSVEP latency increases seen during the study interval. Four eyes decreased in latency by 10 msec or more during the study interval. All these eyes had had an episode of acute optic neuritis which began in the 5 weeks immediately preceding the 1st PSVEP test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pattern reversal evoked visual potential in the diagnosis of multiple sclerosis.

The pattern reversal evoked visual potential (VEP) was recorded in 37 normal subjects and in 186 patients in whom a diagnosis of multiple sclerosis (MS) was established or suspected. Taking the upper limit of normal as the mean +2.5 SD (111 ms), prolonged latency was found in 75% of definite cases of MS, 58% of probable cases, and 38% of possible cases. A smaller number of patients without prolonged latency had abnormal asymmetry of latency or low amplitude potentials. In patients with a single acute episode of neurological disease resembling MS the incidence of abnormal VEP was very low. In patients examined within three months of an episode of retrobulbar neuritis (RBN), latency was prolonged in 81% of affected eyes, a similar proportion being found in patients with a more remote history of RBN. The importance of establishing the normal for every laboratory engaged on this investigation is emphasised. Prolonged latency of the VEP is common in established MS but has not yet been shown to be a sensitive diagnostic test of the early case.     

Pattern reversal visual evoked potentials in Japanese patients with multiple sclerosis.

Forty-seven Japanese patients with multiple sclerosis, 29 probable (clinically definite) and 18 possible, were studied by black-and-white checkerboard pattern reversal visual evoked potential and were compared with a control group of 20 healthy young adults. The major positive peak (P100) was found to be abnormal in 70% of all cases, 90% of probable cases and 39% of possible cases. P100 was delayed in 38% of all cases and was absent in 23% of all cases. None of the eyes showing a flat pattern response was in the acute stage of optic neuritis. The percentage of cases with no response (23% of all cases) was greater than any of the previously reported series from Western countries, substantiating the previously reported clinical features of oriental multiple sclerosis. The pattern response was absent only when testing eyes with severe visual impairment, whereas delayed latency of P100 was seen regardless of the severity of visual impairment, suggesting the usefulness of P100 latency for detecting subclinical optic nerve lesions.     

Evaluation of visual pathways in multiple sclerosis. I. After-images compared to visual evoked potentials

The value of flight of colours (FOC), i.e. the succession of coloured afterimages following light stimulation, in diagnosing and following visual impairment was evaluated in 65 patients with multiple sclerosis (MS). Previous optimistic reports of the use of a pocket flashlight (PFL) method could not be confirmed, and are ascribed to inadequate methods. An electronic flashlight (EFL) method developed by us, proved a significantly better diagnostic tool (61% abnormal versus 18% abnormal). The EFL method was diagnostically less sensitive than pattern reversal visual evoked potential (PR-VEP) (80% abnormal). It did, however, add to PR-VEP by diagnosing 16 eyes with normal PR-VEP latency. The EFL method reflected the degree of degenerative changes in the central visual pathways and may be of value in following the disease activity in MS. The potential of the EFL method may be further improved by proposed modifications.