Pattern Visual Evoked in Multiple Sclerosis
Responses
James A. Zeese, MD \s=b\ The latency of the first major positive component of the visual evoked response to pattern reversal was measured from a midoccipital electrode for each eye in 30 patients with a definite diagnosis of multiple sclerosis (MS). Their latencies were compared with those of a group of 18 normal subjects and 18 patients with
other
neurological diseases. Of 26 MS patients with a measurable response, 77%
gave values that were outside the ranges of the two control groups. A total of 75% of the MS patients without history or findings of optic neuritis had an abnormal response. The procedure appears to be useful in detecting asymptomatic lesions of the visual pathways in suspected MS
patients. (Arch Neurol 34:314-316, 1977) al'·'-' have Halliday the latency the
shown that first major of the visual positive component evoked response to pattern reversal falls within a narrow range in normal subjects and that this latency is often prolonged following optic neuritis and in patients with multiple sclerosis (MS), both with and without a history or findings of optic neuritis. Asselman et al* have obtained similar results with control subjects and MS patients. Since the diagnosis of MS depends largely on clinical observations indi¬ cating multiple CNS lesions, these investigators have proposed the pat¬ tern evoked response as an objective means of identifying lesions of the visual pathways. This study compares the pattern evoked response in (1) patients with a definite diagnosis of MS, (2) normal subjects, and (3) et
of
with neurological diseases the cerebral hemispheres other than MS.
patients affecting
SUBJECTS AND METHODS
Thirty patients meeting McAlpine
No. 4 7 1 4 1 1
Parkinson disease Seizure disorder
Extrapyramidal syndrome
Stroke Transient ischemie attack Dementia (senile)
A checkerboard pattern of light and dark squares was projected via a mirror on the back of a translucent screen 1 m in front of the subject. The pattern subtended an angle with the eye of 30 degrees, with each square subtending an angle of 45 minutes. The pattern was shifted side to side every 0.6 seconds such that the light and dark squares reversed position by shifting the mirror to and fro. The mirror was driven by a trapezoidal shaped signal with rise and fall times of 10 msec such that the reversal of the pattern took 10 msec, with the pattern then remaining stationary for
Comparison of
for
1975.
Reprint requests to Department of Neurology, University of Minnesota Hospitals, Minneapolis, MN 55455 (Dr Zeese).
screen,
and each eye
was
stimulated sepa¬
rately, with the other eye being covered. At
least two trials were done for each eye, and the mean latency of the first major positive component for the trials was calculated. The responses were measured from a midline occipital electrode 5 cm above the inion referenced to a midline electrode 12 cm behind the nasion.
RESULTS
Figure 1 shows typical pattern evoked responses for three different normal subjects. Although there are variations in the minor components of the responses, the first major positive (downward) component is easily iden¬ tified. The mean latency for 18 normal subjects
was
103.3
msec
(SD, 3.2;
range, 95.4 to 108.3). Eighteen control patients with neurological diseases other than MS showed similar responses. The mean latency of the first major positivity for the control
was 110.1 msec (SD, 6.5; range, 100.3 to 123.5). Figure 2 shows typical evoked responses for three patients with MS, all with visual acuity of 20/30 or better. The first two patients had no history of optic neuritis, although
patients
Latencies Between Three
Groups of Subjects
No.
>That ol Normal Subjects
(%) With Latency >Thaf of Control Patients
Multiple sclerosis (MS) patients with measurable response (N 26)_24 (92)_19 (73) MS patients without history of optic neuritis (N 16)_15 (94)_12 (75) MS patients without findings of optic neuritis (N 8)_7(88)_6(75) MS patients with history neuritis 7(70) of optic 9(90) (N 10) =
publication Feb 2, 1977. From the Department of Neurology, University of Minnesota Hospitals, Minneapolis. Read in part before the annual meeting of the American EEG Society, Mexico City, Oct 17, Accepted
and
co-workers'* criteria for definite MS were studied. Their mean age was 41.3 years (range, 25 to 66). Eighteen normal subjects with a mean age of 30.4 years (range, 21 to 62) and 18 patients with a mean age of 46.7 years (range, 21 to 73) with diagnosed neurological diseases affecting the cere¬ bral hemispheres other than MS, but with normal corrected visual acuity, were also studied. The diagnoses of the control patients are shown below:
period. Timing signals were produced to trigger an averaging computer each time the pattern reversed position, and the response to 200 reversals was averaged. A point for fixation was provided in the center of the the remainder of the 0.6 second
=
=
=
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 06/12/2015
J_I_I
msec
msec
Fig
Fig 1 —Pattern evoked responses for one eye of three normal subjects, showing consistency of first major positive (downward)
2.—Pattern evoked responses for
one
eye of three is
patients with multiple sclerosis. Positive component downward; negative is upward.
component.
1 had bilateral optic atrophy. Patient 3 had a history of bilateral optic neuritis. If visual acuity is very poor, it is difficult to obtain a response. The first two responses shown in Fig 3 are from a patient who had a history of optic neuritis of the right eye and optic atrophy with a visual acuity of 20/200. The left eye was normal on examination and had a visual acuity of 20/30. The right eye shows a poorly defined positivity at about 215 msec, and the left eye shows a well defined positivity at 139 msec. The third response is from a patient with optic neuritis and secondary optic atrophy, with visual acuity limited to finger counting. Although this response was
patient
fairly repeatable on separate trials, no definite major positivity can be iden¬ tified. Of the 30 patients with a diag¬ nosis of MS, 26 had a measurable response.
Figure 4 shows the distribution of latencies for the three groups, plot¬ ting the value for the eye with the longer latency of each subject. Com¬ parisons between the three groups are shown in the Table. Ninety-two per¬ cent of the MS patients had a longer
latency than the normal subjects, and 73% were longer than the patients with other neurological diseases. Six¬ teen of the MS patients had no history of optic neuritis, and of these, 94% had a longer latency than the normal subjects and 75% were longer than the control patients. Eight MS patients had no clinical findings of optic neuri¬ tis, and 88% of these had a longer latency than the normal subjects and 75% had a longer latency than the control patients. Among the control patients, no correlation with age or diagnosis was found to explain the
differences in latencies between this group and the normal subjects. In addition to the absolute value of the latency, the difference of the latencies between eyes may be of value in discriminating between a normal and abnormal response. The mean difference of latencies between eyes (left minus right) for normal subjects was 0.9 msec (SD, 2.0) and for control patients, 1.3 msec (SD, 1.9). It would thus be expected that 99% of subjects in these groups would have a difference between the two eyes of less than 7 msec. Of the 26 MS patients with a measurable response,
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 06/12/2015
difference between the two greater than 7 msec. It should be noted, however, that in MS patients with relatively long latencies, the waveform is often not as well defined as in normal subjects and it is more difficult to get exactly repeatable trials. Thus, with long latencies, mild differences between the two eyes are more likely to be seen. Of the seven MS patients with latency equal to or less than that of the control patients, one had a difference between the two eyes of greater than 7 msec. Thus, using this measure as well as the absolute values of latency, 20 (77%) of the MS patients with a measurable response were different than either the control patients or normal sub¬ 14 had eyes of
a
jects.
Ten of the MS patients with a measurable response (Table) had a history of optic neuritis. Of these, one patient had latencies that fell within the range of that of normal subjects, although the amplitude of the re¬ sponse for the previously affected eye was considerably less (32%) than that of the unaffected eye. In general,
however, amplitude are
much
more
measurements
variable than latencies
250 No
4,
R eye VA = 20/200
No.
4,
L eye
VA
=
20/30
200 o > «
No.
5,
R eye
VA
=
FC
400 msec
Fig 3.—Pattern evoked responses for two patients with multiple sclerosis. Patient 4 has poorly defined major positivity for right eye. Patient 5 has no definable major positivity. Positive component is downward; negative is upward. VA indicates visual acuity; FC, finger counting.
Fig 4.—Distribution of latencies three different subject groups.
(eye with the longer latency) for
of the first major positive component and are particularly sensitive to drow¬ siness and/or inattention to the sub¬ ject. Two additional patients with a history of optic neuritis had latencies that fell into the range of that of the control patients, although one of them
had a significant (P < .01) asymmetry of 14.8 msec between the two eyes.
COMMENT The results indicate that the pat¬
tern visual evoked response should be
useful aid in the diagnosis of multiple sclerosis because of its ability to detect asymptomatic lesions of the visual pathways. The percentage of MS patients in this study that show
a
abnormalities of pattern visual evoked responses is similar to that reported by others.2 ' The high per¬ centage of delayed responses follow¬ ing optic neuritis and the frequent asymmetrical delays in MS patients suggest that the lesion producing the abnormality is demyelination in the optic nerve itself. Nevertheless, a
central effect related to hemispheral disease may play a role in the delayed latencies, as evidenced by the mild delays in many of the control patients when compared to the latencies of the normal subjects. Previous reports have not included in their control groups patients with diagnosed neuro¬ logical diseases affecting the cerebral hemispheres other than MS. It must be stressed that prolonged latencies are not specific for optic neuritis since diseases of the eye as well as compressive lesions of the
optic
give delayed responses, the latter having been recently studied in detail by Halliday et al.5 In addition, degenerative neu¬ rological diseases that affect the visual pathways may also give abnor¬ nerves
may
mal responses.2 At the University of Minnesota Hospitals, the test has often proved useful in confirming abnormalities in patients with histories or findings that are only suggestive of optic neuritis. In addition, the test has been
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 06/12/2015
helpful in making the diagnosis of MS in patients with history and clinical findings indicating disease mainly in the posterior fossa structures and/or spinal cord, particularly when the findings have been present for several
years. The ultimate usefulness of the test in cases such as these awaits the passage of time to see how many of these patients will eventually meet the usual clinical criteria or the
autopsy findings indicative of MS. References 1. Halliday AM, McDonald WI, Mushin J: Delayed visual evoked response in optic neuritis.
Lancet 1:982-985, 1972. 2. Halliday AM, McDonald WI, Mushin J: Visual evoked response in diagnosis of multiple sclerosis. Br Med J 4:661-664, 1973. 3. Asselman P, Chadwick DW, Marsden CD: Visual evoked responses in the diagnosis and management of patients suspected of multiple sclerosis. Brain 98:261-282, 1975. 4. McAlpine D, Lumsden CE, Acheson ED: Multiple Sclerosis: A Reappraisal. Edinburgh, Churchill Livingstone, 1972. 5. Halliday AM, Halliday E, Kriss A, et al: The pattern-evoked potential in compression of the anterior visual pathways. Brain 99:357-374, 1976.
Responses
James A. Zeese, MD \s=b\ The latency of the first major positive component of the visual evoked response to pattern reversal was measured from a midoccipital electrode for each eye in 30 patients with a definite diagnosis of multiple sclerosis (MS). Their latencies were compared with those of a group of 18 normal subjects and 18 patients with
other
neurological diseases. Of 26 MS patients with a measurable response, 77%
gave values that were outside the ranges of the two control groups. A total of 75% of the MS patients without history or findings of optic neuritis had an abnormal response. The procedure appears to be useful in detecting asymptomatic lesions of the visual pathways in suspected MS
patients. (Arch Neurol 34:314-316, 1977) al'·'-' have Halliday the latency the
shown that first major of the visual positive component evoked response to pattern reversal falls within a narrow range in normal subjects and that this latency is often prolonged following optic neuritis and in patients with multiple sclerosis (MS), both with and without a history or findings of optic neuritis. Asselman et al* have obtained similar results with control subjects and MS patients. Since the diagnosis of MS depends largely on clinical observations indi¬ cating multiple CNS lesions, these investigators have proposed the pat¬ tern evoked response as an objective means of identifying lesions of the visual pathways. This study compares the pattern evoked response in (1) patients with a definite diagnosis of MS, (2) normal subjects, and (3) et
of
with neurological diseases the cerebral hemispheres other than MS.
patients affecting
SUBJECTS AND METHODS
Thirty patients meeting McAlpine
No. 4 7 1 4 1 1
Parkinson disease Seizure disorder
Extrapyramidal syndrome
Stroke Transient ischemie attack Dementia (senile)
A checkerboard pattern of light and dark squares was projected via a mirror on the back of a translucent screen 1 m in front of the subject. The pattern subtended an angle with the eye of 30 degrees, with each square subtending an angle of 45 minutes. The pattern was shifted side to side every 0.6 seconds such that the light and dark squares reversed position by shifting the mirror to and fro. The mirror was driven by a trapezoidal shaped signal with rise and fall times of 10 msec such that the reversal of the pattern took 10 msec, with the pattern then remaining stationary for
Comparison of
for
1975.
Reprint requests to Department of Neurology, University of Minnesota Hospitals, Minneapolis, MN 55455 (Dr Zeese).
screen,
and each eye
was
stimulated sepa¬
rately, with the other eye being covered. At
least two trials were done for each eye, and the mean latency of the first major positive component for the trials was calculated. The responses were measured from a midline occipital electrode 5 cm above the inion referenced to a midline electrode 12 cm behind the nasion.
RESULTS
Figure 1 shows typical pattern evoked responses for three different normal subjects. Although there are variations in the minor components of the responses, the first major positive (downward) component is easily iden¬ tified. The mean latency for 18 normal subjects
was
103.3
msec
(SD, 3.2;
range, 95.4 to 108.3). Eighteen control patients with neurological diseases other than MS showed similar responses. The mean latency of the first major positivity for the control
was 110.1 msec (SD, 6.5; range, 100.3 to 123.5). Figure 2 shows typical evoked responses for three patients with MS, all with visual acuity of 20/30 or better. The first two patients had no history of optic neuritis, although
patients
Latencies Between Three
Groups of Subjects
No.
>That ol Normal Subjects
(%) With Latency >Thaf of Control Patients
Multiple sclerosis (MS) patients with measurable response (N 26)_24 (92)_19 (73) MS patients without history of optic neuritis (N 16)_15 (94)_12 (75) MS patients without findings of optic neuritis (N 8)_7(88)_6(75) MS patients with history neuritis 7(70) of optic 9(90) (N 10) =
publication Feb 2, 1977. From the Department of Neurology, University of Minnesota Hospitals, Minneapolis. Read in part before the annual meeting of the American EEG Society, Mexico City, Oct 17, Accepted
and
co-workers'* criteria for definite MS were studied. Their mean age was 41.3 years (range, 25 to 66). Eighteen normal subjects with a mean age of 30.4 years (range, 21 to 62) and 18 patients with a mean age of 46.7 years (range, 21 to 73) with diagnosed neurological diseases affecting the cere¬ bral hemispheres other than MS, but with normal corrected visual acuity, were also studied. The diagnoses of the control patients are shown below:
period. Timing signals were produced to trigger an averaging computer each time the pattern reversed position, and the response to 200 reversals was averaged. A point for fixation was provided in the center of the the remainder of the 0.6 second
=
=
=
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 06/12/2015
J_I_I
msec
msec
Fig
Fig 1 —Pattern evoked responses for one eye of three normal subjects, showing consistency of first major positive (downward)
2.—Pattern evoked responses for
one
eye of three is
patients with multiple sclerosis. Positive component downward; negative is upward.
component.
1 had bilateral optic atrophy. Patient 3 had a history of bilateral optic neuritis. If visual acuity is very poor, it is difficult to obtain a response. The first two responses shown in Fig 3 are from a patient who had a history of optic neuritis of the right eye and optic atrophy with a visual acuity of 20/200. The left eye was normal on examination and had a visual acuity of 20/30. The right eye shows a poorly defined positivity at about 215 msec, and the left eye shows a well defined positivity at 139 msec. The third response is from a patient with optic neuritis and secondary optic atrophy, with visual acuity limited to finger counting. Although this response was
patient
fairly repeatable on separate trials, no definite major positivity can be iden¬ tified. Of the 30 patients with a diag¬ nosis of MS, 26 had a measurable response.
Figure 4 shows the distribution of latencies for the three groups, plot¬ ting the value for the eye with the longer latency of each subject. Com¬ parisons between the three groups are shown in the Table. Ninety-two per¬ cent of the MS patients had a longer
latency than the normal subjects, and 73% were longer than the patients with other neurological diseases. Six¬ teen of the MS patients had no history of optic neuritis, and of these, 94% had a longer latency than the normal subjects and 75% were longer than the control patients. Eight MS patients had no clinical findings of optic neuri¬ tis, and 88% of these had a longer latency than the normal subjects and 75% had a longer latency than the control patients. Among the control patients, no correlation with age or diagnosis was found to explain the
differences in latencies between this group and the normal subjects. In addition to the absolute value of the latency, the difference of the latencies between eyes may be of value in discriminating between a normal and abnormal response. The mean difference of latencies between eyes (left minus right) for normal subjects was 0.9 msec (SD, 2.0) and for control patients, 1.3 msec (SD, 1.9). It would thus be expected that 99% of subjects in these groups would have a difference between the two eyes of less than 7 msec. Of the 26 MS patients with a measurable response,
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 06/12/2015
difference between the two greater than 7 msec. It should be noted, however, that in MS patients with relatively long latencies, the waveform is often not as well defined as in normal subjects and it is more difficult to get exactly repeatable trials. Thus, with long latencies, mild differences between the two eyes are more likely to be seen. Of the seven MS patients with latency equal to or less than that of the control patients, one had a difference between the two eyes of greater than 7 msec. Thus, using this measure as well as the absolute values of latency, 20 (77%) of the MS patients with a measurable response were different than either the control patients or normal sub¬ 14 had eyes of
a
jects.
Ten of the MS patients with a measurable response (Table) had a history of optic neuritis. Of these, one patient had latencies that fell within the range of that of normal subjects, although the amplitude of the re¬ sponse for the previously affected eye was considerably less (32%) than that of the unaffected eye. In general,
however, amplitude are
much
more
measurements
variable than latencies
250 No
4,
R eye VA = 20/200
No.
4,
L eye
VA
=
20/30
200 o > «
No.
5,
R eye
VA
=
FC
400 msec
Fig 3.—Pattern evoked responses for two patients with multiple sclerosis. Patient 4 has poorly defined major positivity for right eye. Patient 5 has no definable major positivity. Positive component is downward; negative is upward. VA indicates visual acuity; FC, finger counting.
Fig 4.—Distribution of latencies three different subject groups.
(eye with the longer latency) for
of the first major positive component and are particularly sensitive to drow¬ siness and/or inattention to the sub¬ ject. Two additional patients with a history of optic neuritis had latencies that fell into the range of that of the control patients, although one of them
had a significant (P < .01) asymmetry of 14.8 msec between the two eyes.
COMMENT The results indicate that the pat¬
tern visual evoked response should be
useful aid in the diagnosis of multiple sclerosis because of its ability to detect asymptomatic lesions of the visual pathways. The percentage of MS patients in this study that show
a
abnormalities of pattern visual evoked responses is similar to that reported by others.2 ' The high per¬ centage of delayed responses follow¬ ing optic neuritis and the frequent asymmetrical delays in MS patients suggest that the lesion producing the abnormality is demyelination in the optic nerve itself. Nevertheless, a
central effect related to hemispheral disease may play a role in the delayed latencies, as evidenced by the mild delays in many of the control patients when compared to the latencies of the normal subjects. Previous reports have not included in their control groups patients with diagnosed neuro¬ logical diseases affecting the cerebral hemispheres other than MS. It must be stressed that prolonged latencies are not specific for optic neuritis since diseases of the eye as well as compressive lesions of the
optic
give delayed responses, the latter having been recently studied in detail by Halliday et al.5 In addition, degenerative neu¬ rological diseases that affect the visual pathways may also give abnor¬ nerves
may
mal responses.2 At the University of Minnesota Hospitals, the test has often proved useful in confirming abnormalities in patients with histories or findings that are only suggestive of optic neuritis. In addition, the test has been
Downloaded From: http://archneur.jamanetwork.com/ by a New York University User on 06/12/2015
helpful in making the diagnosis of MS in patients with history and clinical findings indicating disease mainly in the posterior fossa structures and/or spinal cord, particularly when the findings have been present for several
years. The ultimate usefulness of the test in cases such as these awaits the passage of time to see how many of these patients will eventually meet the usual clinical criteria or the
autopsy findings indicative of MS. References 1. Halliday AM, McDonald WI, Mushin J: Delayed visual evoked response in optic neuritis.
Lancet 1:982-985, 1972. 2. Halliday AM, McDonald WI, Mushin J: Visual evoked response in diagnosis of multiple sclerosis. Br Med J 4:661-664, 1973. 3. Asselman P, Chadwick DW, Marsden CD: Visual evoked responses in the diagnosis and management of patients suspected of multiple sclerosis. Brain 98:261-282, 1975. 4. McAlpine D, Lumsden CE, Acheson ED: Multiple Sclerosis: A Reappraisal. Edinburgh, Churchill Livingstone, 1972. 5. Halliday AM, Halliday E, Kriss A, et al: The pattern-evoked potential in compression of the anterior visual pathways. Brain 99:357-374, 1976.
