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Acta
Neurol
Scand
1996 93 246-252
Printed
in
UK
~
all rights reserved Copyright
0
Munksgaard
1996
ACTA NEUROLOGICA
SCANDINAVICA
ISSN
0001-6314
Serial
MRI,
VEP,
SEP
and biotesiometry in
acute optic neuritis: value
of
baseline results
to predict the development of
4
new lesions at
one
year follow up
Frederiksen
JL,
Petrera
J,
Larsson
HBW,
Stigsby
B,
Olesen
J.
Serial
MRI, VEP, SEP and biotesiometry in acute optic neuritis: value of
baseline results to predict the development
of
new lesions at one year
Acta Neurol Scand 1996: 93: 246-252.
0
Munksgaard 1996.
Introduction
-
In an attempt
to
establish the value
of
MRI, VEP, SEP,
and biotesiometry in monitoring disease evolution we undertook a one
year follow up study of 70 untreated patients with acute optic neuritis
(ON).
Muterid
&
methods
-
ON was monosymptomatic in 48 patients
(bilateral in
10)
and part of clinically definite multiple sclerosis (CDMS)
in 22 patients, examined as mentioned below.
Results
~
Results are given
at onset and at follow up (in brackets). In monosymptomatic
ON,
brain
MRI was abnormal in 53% (53%), VEP in the eye with acute ON in 79%
(71%),
VEP in the clinically unaffected eye in 34% (47%), SEP in 25%
(230/0), and biotesiometry in 29% (17%). In CDMS, brain MRI was
abnormal in 95% (95%), VEP in the eye with acute ON
in
86% (77%),
VEP in the clinically unaffected eye in
50%
(64%), SEP in
55%
(So%),
1
and biotesiometry in 63%
(53%).
Only minor changes in test scores were
observed after one year except for significant improvement of VEP in eyes
with acute ON. Eight of 32 patients, characterized by at least one
abnormal paraclinical test at onset of monosymptomatic ON, had
developed CDMS versus none of 16 patients with normal paraclinical
results (p
=
0.03; Fisher).
Conclusion
-
Patients with monosymptomatic
ON
with paraclinical signs of multifocal involvement at onset had an
increased risk
of
developing CDMS. No single test predicted the evolution
of CDMS, perhaps due
to
the relatively short follow up time.
follow up
In the majority of cases acute monosymptomatic
optic neuritis (AMON) is a manifestation of early
multiple sclerosis
(MS)
(1,
2).
In patients with
a single attack and clinical evidence of one lesion,
the diagnosis of laboratory-supported definite
MS
requires paraclinical evidence of another separate
CNS
lesion and
CSF
oligoclonal bands/IgG
(3).
Therefore, laboratory investigations for
MS
may be
tested by their ability to disclose another separate
CNS lesion at the onset
of
AMON
or
their ability
to demonstrate the development of subsequent
lesions during follow
up.
MRI reflects morpholo-
gical abnormalities, while evoked potentials
(EP)
and biotesiometry provide measures of the conduc-
tion in specific
CNS
white matter tracts and provide
J.
L. Frederiksen
',
J.
Petrera
*,
H. B.
W.
Larsson
',
B.
Stigsby
*,
J.
Olesen
'
Departments
of
'Neurology, Glostrup Hospital,
'Clinical Neurophysiology. Gentofte Hospital,
3Magnet~c Resonance, Hvidovre Hospital,
Copenhagen, Denmark
Key
words
MRI;
VEP.
SEP;
vibration; optic neuritis;
multiple sclerosis; follow up studies.
Jette
L
Frederiksen. Department
of
Neurology.
Glostrup University Hospital, DK-2600 Glostrup.
Denmark
Accepted for publication October
26,
1995
information about function of the spinal cord and
the optic nerves, which are not
as
easily visualised
by
MRI
as the brain. Brain
MRI
and the combined
neurophysiological methods yield significantly inter-
related results at onset of AMON
(1).
The present
prospective study compares results at onset and at
one year follow up in
a
cohort of untreated patients
with either
AMON
or acute
ON
as part
of
clinically
definite
MS (CDMS).
We aimed to study if the
two
groups differed with respect to quantitative
changes of MRI,
VEP, SEP,
and vibration percep-
tion thresholds (biotesiometry) and if any para-
clinical findings at onset were significantly predictive
for subsequent progression to
CDMS
within one
year.
246
Serial
MRI,
VEP,
SEP
and biotesiometry
in
ON
Material and methods
Patients diagnosed as
ON
by an ophthalmologist
or a neurologist in the assigned area of Greater
Copenhagen and Zealand were immediately referred
to our study. The final diagnosis of ON was based
on positive clinical criteria and required that other
causes for the visual complaints had been ruled out
by ophthalmological and neurological history and
examination as well as relevant blood tests (4).
Patients with symptoms of ON for more than 28
days, patients with previously ipsilateral
ON,
and
patients with known ethiology of ON other than
CDMS were excluded. Untreated patients were
requested
to
take part in the follow up study, but
33 patients, whereof 16 with CDMS, did either not
comply with two written consecutive requests or
did only complete part of the test battery at follow
up. These patients did not differ according to age,
gender or initial test results from the group of
70
participating patients, nor did their frequency of
development of CDMS differ. In patients who did
not participate in the follow up study, the course
of disease was obtainable from the medical records
supplemented with structured telephone interwiew.
Twenty-two patients (whereof 16 women) aged
12-53 years, median 36 years, had CDMS, as they
had had at least one attack before the actual episode
of acute
ON.
Four of these had had ON in the
contralateral eye, and another 4 patients had bilat-
eral acute ON, defined as simultaneous onset of
ON
within 6 weeks of each other. The remaining
48 patients
(29
women) aged 13-47 years, median
33 years, had AMON, as the neurological history
and examination at onset of
ON
was negative. Of
those, none had previously had ON and ten had
bilateral
ON.
VEP
was performed on the day
of
referral, whereas SEP and biotesiometry were per-
formed within one week from referral, i.e. after a
median of 20 days and 34 days from onset
of
ON,
CDMS and AMON respectively. All but 2 patients
(
1
patient with CDMS was pregnant and one patient
with AMON had a metal pin) underwent brain
MRI after median 12 days in CDMS patients and
26 days in AMON patients from onset of ON. At
follow up from 8 to 18 months (median 12 months)
from onset of
ON
a neurological and ophthalmolo-
gical history and examination, and neurophysiolog-
ical investigations were performed on the same day.
Brain MRI was performed within one week of these
examinations. The local Ethics Committee approved
the study, and the patients gave their informed
consent.
Neurophysiological investigations
Pattern reversal VEP, SEP by stimulating median
and tibia1 nerves, and biotesiometry were performed
with standardised methods used in the department
of clinical neurophysiology
(
1
).
Individual values
were considered abnormal when they exceeded the
mean from healthy controls by three standard devi-
ations
(SD).
For biotesiometry, limits for abnormal-
ity were different for patients below and above forty
years. VEP was additionnally deemed abnormal in
patients with otherwise normal VEP in both eyes,
if the difference in latency between eyes exceeded 8
ms. These methods and the corresponding reference
materials have previously been described including
a quantitative scoring system for each method (1).
On an ordinal scale, a score of
0
represents a normal
test result and maximum abnormality was assigned
a score of 14 for biotesiometry (one point for each
anatomical location tested), 8 per eye for VEP
(based on the PlOO latency, peak-to-peak ampli-
tude, and potential shape), and 20 for SEP (based
on the latency to onset of the cortical SEP, the
central conduction time, and peak-to-peak ampli-
tude), respectively. Reduced amplitudes of VEP and
SEP were only accounted in recordings with pro-
longed latency. Absent VEPs, SEPs and vibration
sense were each assigned the maximum score. In a
previous study of 29 patients with stable MS, VEP
was repeated after one week. The SD of the differ-
ences in PlOO latency between the first and the
second test
of
58 eyes was 6.8, giving a precision
of VEP latency measurements equal to
&
13.6 ms;
95% confidence limit (5). The corresponding VEP
scores were median 2 (0-8) at first examination
and median 2
(0-7)
at the second examination
(0.05
<
p <0.
10;
95% confidence limit) (unpublished
results). Assessment of the test-retest variability of
SEP
in MS has not been done, but for biotesiometry
the mean difference of vibration perception thresh-
olds in persons matched for gender and age
amounted
to
0.15, SD 0.62 (50 healthy controls)
and to 0.41, SD 2.1 (58 patients with MS). These
thresholds pertain to a single anatomical location,
i.e. the second metacarpal bone, where thresholds
between
0
and 50 could be obtained (unpublished
results). All neurophysiological tests were evaluated
by the same investigators (JP and BS), who had no
knowledge of the MRI findings.
MRI
The cerebrum, cerebellum, brainstem, and upper
part of the cervical cord were imaged using a
wholebody MR scanner (Siemens Magneton), oper-
ating at
1.5
Tesla. Two MRI sequences were per-
formed: double spin-echo (24 slices axially) and
inversion recovery
(
10 slices sagittally). Further
details, also with regard to the MRI scoring system
based on number and size of lesions (i.e. grade
0
being normal and grade 6 representing maximum
247
Frederiksen et
al.
abnormality with one of the lesions measuring at
least 15 mm), are given in a previous paper (4). By
estimating slice by slice the length, width and depth
(slice thickness
4
mm)
of
plaques, we quantitated
the total lesion load. Thirty-four healthy volunteers
matched for gender and age without cerebrovascu-
lar risk factors served as control group. A few
minor lesions distributed randomly in the cerebral
hemispheres without predilection to the periventric-
ular regions were revealed by MRI in 5 of 14 (36%)
healthy controls aged 40-55 years, but no lesions
were found outside the brain (6). The MRIs were
all evaluated by the same investigator (HBWL),
who was blinded to the results of the neurophysiol-
ogical investigations.
Statistics
The non-parametric Wilcoxon matched-pairs
signed-ranks test was used to analyse changes within
groups at follow up. Fisher's exact probability test
was used to analyse difference between groups with
regard to development of CDMS.
Results
As listed in Table 1, the frequency of abnormal
results in the various tests were generally higher in
patients with CDMS than in patients with AMON.
From onset to follow up this frequency changed
similarly in both groups. An additional criterion of
abnormality, i.e. differences in VEP latencies
between eyes exceeding 8 ms, increased the number
of
abnormal results
of
VEP from eyes with ON by
2 patients at onset of AMON, and by 2 patients at
follow up in CDMS, and from the fellow eye in
one patient at follow up in CDMS. VEP from eyes
Table
1.
The absolute number and percentage
of
patients with acute optic neuritis,
either monosymptomatic (AMON)
(n=48)
or part of clinically definite multiple
sclerosis (CDMS)
(n=22),
showing abnormality in each
of
the paraclinical tests at
onset and at
1
year follow up. The results
of
VEP in the
fellow
eye
do not include
14
patients with bilateral ON (hereof
10
with AMON) and
4
patients with CDMS
with previous ON in that
eye.
One patient in each group did not undergo
MRI
AMON ON in CDMS
Onset Follow up
Onset
Follow
up
VEP
(eye
with ON)
38 79% 34 71%
VEP (fellow
eye)"
13 34% 18 47%
VEP (in total)
38 79% 34 71%
SEP (median
nerve)
510% 24%
SEP (tibia1 nerve)
10
21% 11 23%
SEP (in total)"
12 25% 11
23%
Biotesiometry"
14 29%
8
17%
Brain
MRI
25 53% 25 53%
Neurophysiology (all")
54%
52%
(all*) and brain
MRI
67%
63%
19
86%
7
50%
19
86%
4
18%
12 55%
12
55%
11
50%
77%
100%
20
95%
17 77%
7
50%
17 77%
5
23%
10
45%
11
50%
11 50%
21 95%
68%
95%
with acute ON improved significantly in patients
with AMON, and normalised at follow up in
5
of
38 patients with AMON and in
5
of
19
patients
with CDMS. The development of abnormal VEP
from the fellow eye could only be explained by
development of acute ON during follow up in one
of
6 patients with AMON and one of 2 patients
with CDMS. The frequency of abnormal results
of
SEP and biotesiometry was the same, both at onset
and follow up. A lesion in the cerebellum or brain-
stem was only observed in one patients with CDMS.
A cervical cord lesion as the only MRI abnormality
was observed in one patient with AMON and in
one patient with CDMS. Regarding the specificity
of MRI in our 13 patients with AMON aged 40-47
years, 6 had abnormal MRI at onset and
6
at follow
up, and only two at onset and one at follow up had
less than
7
lesions. The results mentioned below
refer to patients with AMON, and to patients with
CDMS (in brackets). Combined neurophysiological
investigations, apart from VEP from fellow eyes
with previous or present
ON,
showed one or more
abnormal results in 26/48
=
54%
(
17/22
=
77%) of
patients at onset versus 25/48
=
52%
(
15/22
=
68%)
at follow up.
By
adding the result of brain MRI,
the frequency of any abnormality increased to
32/48
=
67% (22122
=
100%) at onset and 30148
=
63% (21/22
=
95%) at follow up. The overall abnor-
mal neurophysiological results except for VEP from
eyes with previous or present
ON
were observed in
3
of
48
(6%)
patients with AMON and in
4
of 22
(18%) of patients with CDMS, both at onset and
at follow up. These patients, apart from one patient
at onset
of
AMON, also had abnormal brain MRI.
In unilateral AMON, one or more abnormal results
of VEP from the fellow eye, SEP, and biotesiometry
were observed at onset in 24 of
38
patients (i.e
63%). The number of patients increased to
28
of 38
(i.e. 74%), when the result
of
brain MRI was added.
These number were unchanged at follow up.
At re-examination,
8
of
48
patients
(4
women; 2
bilateral ON) aged 13-38 years, median 22 years,
with AMON had developed CDMS. Those patients
all belonged to the subgroup of 32 patients with
one or more abnormal results (excluding
VEP
from
eyes with acute
ON)
at onset. As can be deducted
from Table 2, the MRI lesion load and the frequency
of abnormal results of single tests, apart from SEP,
tended to be higher in the group of patients who
developed CDMS than in the remaining patients.
The risk of developing CDMS, i.e.
8
of 32 patients
with abnormal versus none of
16
patients with
normal paraclinical findings (except for VEP from
the eyes with ON) at onset, was significantly
increased (p
=
0.03, Fisher's exact probability test,
one-tailed). The probability of progression to
CDMS after abnormal results of a single test at
248
Serial
MRI,
VEP, SEP and biotesiometry in
ON
Table
2
Quantitative scores obtained from paraclinical tests at onset
of
monosymptomatic
ON
(upper line) and at follow
up
[lower
line] in
8
patients, who had developed
clinically definite multiple sclerosis Predictive values of paraclinical tests at onset are listed (VEP score) indicate bilateral
ON
at onset
Sex
M
F
F
F
M M
F
M
Predictive
Age
(years)
22
32 15
20
26
13
22
38
value
(%)
VEP
(eye
with
ON)
4
VEP (fellow
eye)
(4)
SEP
(in
total)
0
Biotesiometry
0
0
0
0
0
Brain MRI
6
1
MRI
lesion load
1917
(mm?
47 1
2
3
6
3
4
6
0
(3)
4
2
4
6
0
2
2
0
0
0
0
2
0
0
2
0
1 1 1
1 1
3
77 141 201
77 318 1162
1
5
0
0
0
0
1
0
0
3
0
1124
8
5
4 5
1
0
2
4
0 0
0 0
0
10
0
3
0
4
0
4
0
2325
0
2325
4
pos
1
0
2/13
0
(=15%)
0
2/12
0
(=17%)
0
3/14
0
(=21%)
6
6/25
6
(=24%)
707
707
neg.
21/25
30136
(=83%)
29/34
19/22
(
=
86%)
(
=
84%)
(=
85%)
onset, i.e. positive predictive value, and the probab-
ility of non-progression to CDMS after normal
results of a single test at onset, i.e. negative predict-
ive value, are listed. No single test had significant
predictive value. Table
3
shows the median and
range of the test scores. The values were generally
lower in patients with AMON than in patients with
CDMS. Within groups no significant changes of
scores were observed between onset and follow up,
except for a significant improvement of
VEP
in the
affected eyes in AMON. The median brain MRI
lesion load increased insignificantly in both groups.
These findings were similar, when the two groups
were combined.
Discussion
In
1991
we published a study of MRI,
VEP, SEP
and biotesiometry in acute monosymptomatic optic
neuritis (AMON) related to the results to previous
investigations
(1).
It is tempting to suggest that
patients with subclinical lesions revealed by the
above-mentioned paraclinical tests at onset of
AMON are more likely to develop clinically definite
multiple sclerosis (CDMS). However, only a few
prospective studies and none with serial examina-
tions of
SEP
and biotesiometry, have been carried
out to test this hypothesis. We performed a one
year follow up of a representative, homogeneous
group of untreated patients with AMON or ON
as
part of CDMS with the above-mentioned quantitat-
ive methods. Compared with previous studies, the
present study has one or more advantages: the
number of patients is higher, they were all untreated,
and examined prospectively with a greater battery
of quantitative tests, and exclusion of patients with
other causes of
ON
were based on extensive screen-
ing. Further, the first examination took place a few
weeks from onset of symptoms and the follow up
time variation was small. The value of each test to
measure deterioration and to predict development
of CDMS is discussed.
VEP
The test-retest variability of the
VEP PlOO
latency
in healthy controls and in CDMS is small, implying
that even small changes between recordings may be
of diagnostic value
(5,
7,
8).
Several studies have
re-examined patients with AMON or ON as part
of CDMS, characterized by abnormal
VEP
at onset,
with
VEP
at least one year from onset
(9-16).
Most
Table
3.
The median and range of scores for each
of
the paraclinical tests performed at onset and at one year follow up in
70
patients with acute optic neuritis, either
monosymptomatic (AMON)
(n=48)
or
pait
of
clinically definite multiple sclerosis (CDMS)
(n=22)
The mean and range depicted for VEP in
the
fellow
eye
do not include
14
patients with bilateral
ON
(hereof
10
with AMON) and
4
patients with CDMS with previous
ON
in that
eye.
The median brain
MRI
lesion load in
mm3
is also shown.
Results of Wilcoxon matched pairs signal-rank test for changes of scores during one year
of
follow up are listed
AMON ON IN CDMS All ON
Onset Follow up
P
Onset Follow up
P P
VEP
(+ON
eye)
3
(0-8)
2
(0-8)
i
0.05
3
(0-8)
4
(0-8) >0.05
10
05
SEP
0
(0-9)
0
(0-12) >0.4
3
(0-16) 1 (0-14)
>
0.4
>
0.4
Biotesiometly
0
(0-14)
0
(0-14) >0.05
1
(0-14)
1
(0-14)
>
0.4 >04
VEP
(-ON
eye)
0
(0-6)
0
(0-6)
>
0.1
0
(0-6)
0
(0-8)
>0.4 >O.l
Brain
MRI
1
(0-6)
1
(0-6)
>0.4
3
(0-6)
3
(0-6)
>
0.4
>0.2
Brain
MRI
lesion
28
157 r0.1 318 664
>02
=0.1
load
(mm3)
(0-4081) (0-41
42)
(0-6636)
(0-6735)
Frederiksen
et
al.
studies comprised small and mixed study popula-
tions with considerably variation in follow up length
and they only classified the results into normal or
abnormal. In the single study greater than ours,
VEP normalized in 15% of
80
patients followed
median 46 months (6-120 months)( 12). The fre-
quency of normalization of VEP varied from
5%
to
35% in the remaining studies (9-11, 13-16), in line
with 13% in AMON and 26% in CDMS in the
present study. Our findings of a normal VEP in
eyes with acute
ON
in 21% of patients with AMON
and in 14% of patients with CDMS might be due
to a very short interval from onset of
ON
to VEP
recording in some patients, and to referral of
patients with only minor symptoms
(
1, 17). Only 6
of our 38 (16%) patients with unilateral AMON
developed CDMS within one year of follow up
compared to 29 of 48 (60%) ‘retrospectively’
selected patients followed for 0.5 to 3.5 years and
characterized by unilateral
ON
and abnormal VEP
at onset (18).
SEP
and biotesiometry
In three smaller studies, the test-retest variability of
latency of the median nerve SEP in healthy controls
was small (19-21). The tibial nerve SEP variability
was markedly greater (20). Amplitudes showed a
considerably greater variability than latency
to
onset (21). In patients with CDMS, SEP was useful
for monitoring of changes in time
(
19). Serial
prospective studies of SEP and biotesiometry in
AMON have not previously been published. Of 39
patients examined at onset of unilateral retrobulbar
AMON, cortical and cervical SEP was abnormal in
4 patients
(1
developed CDMS) and normal in 35
patients (2 developed CDMS) (22). The sensitivity
of SEP might have increased, if tibial nerve stimula-
tion had been performed (23). Although SEP and
BAEP were normal in all patients with AMON,
5
of 15 patients developed MS within an average of
33 months (12-56 months) (24). Abnormal SEP
was found in 4 of 20 patients with ON, but none
developed CDMS within
1
year (25). SEP is appar-
ently unlikely to be helpful predicting CDMS in
patients with AMON. Either
is
the method insensit-
ive or there are no subclinical plaques in the sensory
pathways (22, 24, 25). We did not perform MRI of
the whole spinal cord. By re-examining the patients
we found that fluctuations in neurophysiological
parameters may occur independently from clinical
evolution. We did not perform BAEP, as this has
not been of major utility in our clinical experience
nor in most studies of patients with AMON (23,24,
26, 27). Probably asymptomatic brainstem lesions
are rare as also found with MRI (4, 28, 29).
MRI
In the present study, the frequency of abnormal
brain MRI did not change and the median brain
MRI lesion load did not increase significantly. Of
34 patients with abnormal MRI at onset of AMON,
12 patients developed MS, in 5 patients accompan-
ied of new MRI lesions (30). None of the 19
patients with normal MRI developed CDMS, but
new subclinical lesions appeared in 3 during 4-24
months, median
11
months, of follow up. At 2-year
follow-up 36% of placebo-treated patients whose
initial MRIs revealed two or more lesions sized
3mm or more developed MS, compared with 3%
of patients with normal MRI (3
1
).
During 2-186
months, mean 4 years, of follow up CDMS had
developed in 26% patients with abnormal MRI and
in 12% patients with normal MRI at onset of
AMON (29). This difference was not significant.
During
5
years of follow up, 82% of patients with
abnormal MRI and 6% of patients with normal
MRI at onset of clinically isolated ON developed
CDMS (32). In a mixed population of 84 patients
with clinically isolated syndromes suggestive of MS,
whereof 40 patients presented with ON, the 34
patients developing CDMS during
5
years of follow
up had a higher lesion load at presentation than
the patients who remained monosymptomatic.
There was a correlation of the initial MRI lesion
load with the increase in lesion load over the next
5 years and with a decreasing time to development
of
MS clinically (33). Thus, the prognostic signific-
ance of MRI findings seems to increase with length
of follow up.
Combination
of
MRI
and neurophysiological investigations
No previous investigations adresses whether re-
peated SEP and biotesiometry examinations are
useful to reveal asymptomatic lesions in AMON.
Correlation between neurophysiological data and
MRI has only been performed at onset of
ON.
Paty
et al. published a multimodality
EP
study including
MRI in
200
patients with MS or related diseases,
whereof 38 patients with
ON
(34). A 2-year follow
up study was published, but the course of ON
patients was unfortunately not specified. Of 21
patients examined median 36 days from onset of
ON, VEP was abnormal in 62% of affected eyes
and in 15% of unaffected eyes and MRI was abnor-
mal in 38%. Only one patient developed CDMS
within a mean follow up of 2.9 years, but serial
scanning of 17 patients revealed new subclinical
lesions in 3 patients (35). Of 43 patients with
AMON, the majority treated with oral steroid,
brain MRI was abnormal at onset in 21 patients
(7
developed CDMS) and SEP in
5
patients (2
250
developed CDMS) (23). Within a mean of 32
months, 7 of 37 patients (19%) developed CDMS,
similar to our findings within median one year.
However, we observed development of CDMS also
in patients who initially had normal MRI.
Introduction of a total score for each test repres-
ents a data reduction procedure that might have
made the test results less sensitive to changes than
if each partial measurement, for example latency of
EPs were compared directly. However, by introdu-
cing a scoring system for EPs we overcame the
difficulties in dealing with aberrant wave forms and
absent EPs.
A
VEP exhibiting a bifid or ‘W’ mor-
phology was frequently encountered in our patients
and could have the clinical significance as a delayed
PlOO latency (36). As was the case with VEP, the
additional use of right-left differences by SEP and
biotesiometry in our study might have increased the
sensitivity, but those procedures are not routine in
our standardised methods.
In conclusion, overall abnormal neurophysiolog-
ical results in single patients were seldomly
observed, but by combining different neurophysiol-
ogical procedures the proportion of abnormal find-
ings in AMON increased to a similar level as found
for MRI. In AMON, brain MRI and neurophysiol-
ogical tests were complementary in revealing sub-
clinical lesions. One abnormal paraclinical finding
at onset of AMON is enough to increase the risk
of developing CDMS within one year of follow up.
None of the applied tests were, however, isolated
able to predict whether CDMS would develop,
presumeably because the length of follow up were
not large enough to reach statistical significance.
This implies that not only MRI, but also a battery
of neurophysiological tests should be used
to
mon-
itor the disease evolution in treatment trials of
patients with AMON. We observed a small dynamic
range of the scoring systems with minor changes
from onset to follow up after one year, but the
usefullness of MRI and neurophysiological methods
may well be greater when evaluated at a 5-year
follow up. Such a study is in progress.
Acknowledgements
The authors are indebted to the technical assistants of the
Department of Clinical Neurophysiology, Gentofte Hospital,
for performing VEP, SEP and biotesiometry. We acknowledge
gratefully the members of the Copenhagen Acute MS Study
Group and neurologists and ophthalmologists in the assigned
area of Greater Copenhagen and Zealand for referring the
patients. This investigation was supported by the Danish
Multiple Sclerosis Foundation and the Warwara Larsen
Foundation and the Foundation of Sigurd Abrahamson and
wife.
Serial
MRI,
VEP,
SEP
and biotesiometry in
ON
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