Provoked visual impairment in multiple sclerosis studied by visual evoked responses.

Pattern-reversal VERs were studied during the visual impairment provoked by exercise in 2 patients with demyelinating optic neuritis. It was found that the transient reduction in visual acuity was correlated to a transient decrease in the amplitude of the major positive component of the VER, whereas no significant changes could be observed in the latency of the response. The normal VER was not influenced by exercise.     

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     

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.     

Effect of raising body temperature on visual and somatosensory evoked potentials in patients with multiple sclerosis.

The effects of raising body temperature on the visual (VEP) and somatosensory (SEP) evoked potentials were observed in normal subjects and in patients with multiple sclerosis. The amplitude of the VEP was significantly reduced to the same degree after heating in normal subjects and in patients with multiple sclerosis but there was no effect on the latency of the potential. Changes in amplitude could not be related to reduction in acuity. In contrast, the cervical SEP was greatly disorganised after heating in many patients with multiple sclerosis while the only effect in normal subjects was to reduce the latency by increasing peripheral conduction velocity. These results suggest that heat caused conduction block in demyelinated axons in the sensory pathways of the cervical spinal cord.     

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.     

Visual and somatosensory evoked cortical potentials in multiple sclerosis.

The diagnostic value of the pattern reversal evoked cortical potential (VEP) and the somatosensory evoked cortical potential (SEP) has been compared in 50 patients with established or suspected multiple sclerosis. A prolonged latency of VEP was found in 96% of definite cases of multiple sclerosis, 58% of probable cases, and 20% of possible cases. A prolonged latency of SEP by stimulation of median or peroneal nerves or both was found in 86% of definite cases of multiple sclerosis, 83% of probable cases, and 50% of possibe cases. When combining the results of all three tests the diagnostic yield increased to 100%, 92%, and 50%, respectively.     

Cortical somatosensory magnetic responses in multiple sclerosis.

Somatosensory evoked magnetic fields (SEFs) to contralateral median and ulnar nerve stimulation were analyzed in 10 patients with multiple sclerosis and in 8 healthy controls. SEFs were recorded with a 24-channel SQUID gradiometer over both hemispheres. Seven patients showed abnormally large-amplitude SEF deflections at 60-80 msec; 5 of them had multiple lesions around lateral ventricles in magnetic resonance imaging. In 2 patients with plaques at the level of 3rd and 4th ventricles and medulla, the 30 msec responses were enlarged. The equivalent sources of 20 msec and 30-80 msec responses were in the primary hand sensorimotor cortex both in patients and in control subjects. The results suggest that early and middle-latency SEFs reflect parallel processing of somatosensory input. Recording of middle-latency evoked responses, electric or magnetic, may give additional information about the somatosensory function in 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.     

Magnetic stimulation motor evoked potential in multiple sclerosis. Comparison with visual evoked potentials, brain stem auditory evoked potentials and somatosensory evoked potentials]

This study consists of 45 patients with clinically definite MS, laboratory supported definite MS and clinically probable MS. We compared MEP results with other multimodal evoked potentials (VEP, BAEP and SEP). The abnormal rate of MEP was 87.6%, which was the highest. Abnormal MEP showed prolonged central motor conduction time (CMCT), consistent with pathological change of the demyelination. There was a evident correlation between the abnormal MEP and VEP, which is consistent with the most common MS (Devic Syndrome) in our country.     

Visual evoked responses and immunoglobulin abnormalities in the diagnosis of multiple sclerosis

Visually evoked responses (VERs), CSF IgG/albumin ratio and CSF oligoclonal IgG were examined in 136 patients with multiple sclerosis (MS) admitted to hospital for investigation, and compared to the CSF findings in 87 patients with other neurological diseases (OND). 33% of patients with OND had abnormal CSF IgG/albumin ratios but only 9% had CSF oligoclonal IgG banding. In clinically definite MS, VERs were abnormal in 87% and CSF oligoclonal banding was found in 80% of patients, but CSF oligoclonal banding was found significantly more frequently than abnormal VERs in patients with suspected MS. We were unable to show any relationship between benign MS and the absence or presence of CSF oligoclonal IgG. The significance of CSF oligoclonal IgG in the less clinically definite forms of MS will only emerge with prolonged follow-up.     

The value of brain stem auditory, visual and somatosensory evoked potentials and blink reflexes in the diagnosis of multiple sclerosis

Cervical and cortical somatosensory evoked potentials (SEP) following electrical stimulation of the median nerve and blink reflexes (BR) following electrical stimulation of the supraorbital nerve were recorded in 30 normal subjects aged 20–49 years. Subjects aged 40–49 had longer SEP latencies than subjects aged 20–39 years.
A total of 29 slightly affected patients with multiple sclerosis (MS) aged 26–49 years, including four patients without clinical signs (suspected MS) and 19 patients with signs indicating only one lesion (possible MS) were examined by low-rate random-stimulated brain stem auditory (BAEP), checkerboard pattern-reversal visual evoked potentials (VEP), SEP and BR. Abnormal recordings by at least one of the examinations were found in all but three patients, and by all four tests in five patients.
In patients with definite or probable MS, demonstration of clinically recognized or subclinical lesions was of minor diagnostic value, in contrast to the importance such findings had in patients with suspected or possible MS. Silent lesions were shown by at least one of the tests in the four suspected and in 13 of the possible MS patients, so these 17 patients could be transferred to a more certain diagnostic category. This reclassification was most often due to the BAEP recording.
In patients with spinal signs, the combination of BAEP and VEP recording was sufficiently efficient. In patients with optic neuritis a combination of BAEP and SEP was preferred. No abnormal recordings were found in 15 normal subjects examined by all four tests.     

The cervical somatosensory evoked potential (SEP) in the diagnosis of multiple sclerosis

Abnormalities of the potential evoked by stimulation of the median nerve and recorded over the cervical spine were found in 59% of patients with multiple sclerosis (MS) this proportion increasing to 69% of those in the definite diagnosis category and to 100% in the severely disabled. Abnormalities were often found in the absence of relevant clinical signs and the method appears to be capable of revealing clinically silent plaques. In patients with a single episode of neurological disease, including retrobulbar neuritis, and at least compatible with the onset of MS, the proportion of abnormalities did not rise above 18%. Only prolonged follow-up will permit assessment of the value of this and other evoked potential techniques in the detection of the early case of the disease.     

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.     

Visual evoked responses in the diagnosis and management of patients suspected of multiple sclerosis.

Averaged visual evoked responses to pattern reversal stimuli have been recorded in 54 control subjects, 51 patients with multiple sclerosis, and 55 patients with other neurological diseases which might involve the visual apparatus. The latency to the peak of the major positive potential in normal subjects under the age of 60 was 104 msec or less (mean 90-5 msec+3 SD). The latency of the VER was prolonged above this value in one or both eyes in 67 per cent of the patients with multiple sclerosis (in 84 per cent of those with definite multiple sclerosis, in 83 per cent of those with probable multiple sclerosis, and in 21 per cent of those with possible multiple sclerosis). The latency of the VER was also prolonged in 25 percent of those with an acute spinal cord lesion of unknown cause; in 46 per cent of those with an isolated brain-stem lesion unknown cause; and in 49 per cent of patients presenting with a progressive spastic paraparesis. The extra delay in latency varied from a few msec to as much as a 100 msec. In patients with multiple sclerosis, a delayed VER was found in the affected eye in all with a previous history of optic neuritis, and in 47 per cent of those with no such history....     

Cortical somatosensory magnetic responses in multiple sclerosis

Somatosenosor evoked magnetic fields (SEFs) to contralateral medium and ulnnar nerve stimulation were analyzed in 10 patients with multiple sclerosis and in 8 healthy controls. SEFs were recorded with a 24-channel SQUID gradiometer over both hemispheres. Seven patients' showed abnormally large-amplitude SEF deflections at 60–80 msec; 5 of them had multiple lesions around lateral ventricles in magnetic resonance imaging. In 2 patients with plaques at the level of 3rd and 4th ventricles and medulla, the 30 msce response were enlarged. The equivalent sources of 20 msec and 30–80 msec responses were in the primary hand sensorimotor cortex both in patients and in control subjects. The results suggest that early and middle-latency SEFs reflect parallel processing of somatosensory input. Recording of middle-latency evoekd responses, electric or magnetic, may give additional information about the somatosensory function in multiple sclerosis.     

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.     

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.