Derzeitiger Forschungsstand zur Diagnose und Behandlung
der Neuritis nervi optici,
sowohl idiopathisch wie auch im Kontext der Multiplen Sklerose:
by Shirley H. Wray.
The linkage between idiopathic optic neuritis and multiple sclerosis (MS) is firmly established.
In the majority of patients, optic neuritis is due to demyelination, whether or not
clinically apparent MS is present. Optic neuritis is predominantly a disease of young
adults. In the New England region of the US, the incidence of optic neuritis in adult
women exceeds that in men by a ratio of 1.8:1. The mean age of onset in women is 30.2
years (range 9-55 years, median 29 years). In men, the mean age of onset is 31.1 years
(range 16-60 years, median 32 years) [l]. The condition is rare in children, in whom
it is usually post- or para-infectious, often simultaneously bilateral and generally
characterized by a good visual prognosis.
Children have a comparatively low risk (35%) of developing MS [5]. Optic neuritis in
patients 40-50 years of age behaves similarly to the disorder in younger
adults (18-39 years of age). In patients over 50 years of age, optic neuritis can be a
misleading diagnosis since other disorders, particularly ischemic optic neuropathy,
commonly cause acute or subacute visual loss.
SYMPTOMS:
LOSS OF VISION:
Decreased visual acuity as an isolated Symptom occurs in 58% of optic neuritis cases.
The rate at which vision falls may be very rapid, within hours (29%); fast, within
1-2 days (20%); slow, within 3-7 days (23%); or even slower, within 1-2 weeks (7%).
Within 7 days of the onset, the visual acuity may be less than 20/60 in 52% of
eyes, 20/70 to 20/100 in 48% and worse than 20/200 in 38 %.
A significant number of eyes continue to lose vision down to an acuity of 20/200 or worse
before stabilizing. EYE PAIN:
The incidence of ipsilateral eye pain in unilateral optic
neuritis ranges from 53% to 88% [1,6].
In one study,it occurred only with eye movements. In 19 pain preceded a decrease
in visual acuity.
115 optic neuritis patients (62%) complained of pain during an attack in or behind
the involved eye. In 39 (21%) it occurred only with eye movements. In 19 (16%)
pain preceded a decrease in visual acuity. Headache in the involved eye
region was reported by 40 patients (22%) and generalized headache by 24
(13%) [6]. Typically, the pain is experienced as a dull ache or sinus pain,
with or without tenderness of the globe. It reaches maximum severity within 24-36
hours and resolves spontaneously within 48-72 hours.
Persistent pain for 7 days is highly atypical and should
prompt a search for other causes of optic neuropathy.
The cause of the eye pain is unknown. It does not correlate with the severity
of visual loss, with the absence of optic disc swelling (which implies retrobulbar
optic neuritis), with enlargement of the optic nerve or with localization of the
demyelinating plaque in the intracanalicular region.
DYSCHROMATOPSIA:
Impaired color vision, dyschromatopsia, is always
present in optic neuritis, characterized by a reduced
vividness of saturated colors. In color terminology,
Saturation refers to the purity of color, and desaturation is the degree to
which a color is mixed with white.
Some patients shown a red target characterize the sensation äs darker,
i.e. red is shifted toward amber, whereas others say the color is bleached or
lighter, i.e. red is shifted towards orange. In the absence of a macular
lesion, color desaturation is a highly sensitive indicator of optic nerve disease.
MOVEMENT- AND SOUND- INDUCED PHOSPHENES:
Movement phosphenes in MS optic neuritis must be distinguished
from phosphenes of retinal origin which are a prelude to retinal detachment.
In optic neuritis, phosphenes occur almost exclusively with horizontal
eye movement, are best perceived in a dark or dimly lit room with the eyes
closed, and appear as a very brief flash of light
lasting only 1 or 2 seconds even if lateral gaze is maintained.
Repeated eye movements cause temporary lulling of the phosphenes with reappearance
after several minutes' rest. They occur unilaterally and ipsilateral to the affected
eye before, during and/or after an attack, and last for as long as 9 months.
Rarely, they may occur 6 months after full recovery, when the visual acuity is
20/20 and fundoscopy is normal. Phosphenes can also be precipitated by sudden noise
when the patient is resting in the dark. They occur transiently in disease
of the eye or of the optic nerve, including optic neuritis and compressive optic
neuropathy.
OBSCURATION OF VISION IN BRIGHT LIGHT: •
Obscuration of vision in bright light is a Symptom of acute optic neuritis.
Patients with chronic optic neuritis in fact see better in dim light. In MS patients
the variability of seeing in different lighting conditions is related to the luminance
of the background, with vision becoming more impaired as background luminance
increases [10]. This luminance-dependent variability is not due to visual fatigue
of the type reported in optic neuritis, but rather to a fluctuating interference in the
Transmission of visual signals along a demyelinated visual pathway
UTHOFF'S SYMPTOM:
Uhthoff's Symptom, episodic transient obscuration of vision with exertion,
occurs in isolated optic neuritis and in MS. The incidence of the Uhthoff-Symptom
in optic neuritis is approximately 50%. Sixteen per cent of patients develop it
within 2 weeks of the onset of visual loss and 58% within 2 months. Such patients may
experience a long period free of the Symptom, e.g. 3-32 months, followed by the
return of episodes without a recurrent attack of optic neuritis. Typically,
the visual obscuration is provoked by 5-20 minutes of brisk exercise.
Acuity becomes blurred and colors desaturated. After a rest period of 5-60 minutes or
up to 24 hours, vision returns to normal. Exertion is not - however - the only
provoking factor for Uhthoff-Symptom. Hot baths or showers account for 27.5% of cases
and hot weather for another 27.5%. HISTORY:
To make a diagnosis of optic neuritis, a meticulo-history
must be taken and it must document: CLINICAL SIGNS:
VISUAL ACUITY:
Subnormal visual acuity must be assessed by measuring best corrected
i.e. best refracted) visual acuity. A pinhole can be used for a reasonable
approximation of best corrected visual acuity. Visual acuity at distance is measured
with a Snellen chart (normal 6/6 m; 20/20 ft). In the fractional denotation,
e.g. 6/60metric (20/200 conventional), the numerator 6 (or 20) stands for the testing
distance (in meters or feet), and the denominator 60 (or 200) stands for the test
letter's size normally seen at that denominator distance. Near
acuity is measured with a near card (Jaeger chart). Bifocals or near spectacles
must be worn by presbyopes (who have difficulty with accommodation) when
testing near vision.
DYSCHROMATOPSIA:
Acquired color vision abnormalities in red/green perception usually imply optic
neuropathy. Color vision defects can be detected clinically using Hardy-Rand-
Ritler or Ishihara pseudoisochromatic plates. More sensitive testing can be achieved
with the Farnsworth-Munsell 100 Hue test. Using this test the author detected
dyschromatopsia in all 23 cases (30 eyes) with optic neuritis, compared to
12/23 cases (13 eyes) tested with Ishihara plates.
Dyschromatopsia was present when visual acuity had recovered to 20/40 or
better [17].
CONTRAST SENSITIVITY:
A triad of Symptoms heralds an acute attack of optic neuritis:
Loss of vision, ipsilateral eye pain and dyschromatopsia. The initial attack is unilateral in 70%
of adult patients and bilateral in 30% [6]. Associated visual Symptoms are movement-
and sound-induced phosphenes, obscuration of vision in bright light and Uhthoff's Symptom.
In asymptomatic patients, mild dyschromatopsia, temporal pallor of the
optic disc and slits in the nerve fiber layer detected on a routine eye examination are
clear signs of the disease. Subclinical cases are also detectable electrophysiologically
by delay of the P 100 potential latency on the visual evoked potential test.
They are also detectable postmortem, as demyelination ofthe optic nerve.
Chronic progressive demyelinating optic neuropathy,
characterized by slowly progressive visual loss without remission, is a rare variant
of optic neuritis.A further variant of chronic progressive demyelinating
optic neuropathy is characterized by slowly progressive loss of visual acuity
punctuated by acute episodes of more profound visual loss and incomplete restoration of vision
after each exacerbation.
In optic neuritis patients, Uhthoff's symptom is a bad prognostic sign:
it correlates significantly with the presence of multifocal white matter
lesions on brain MRI and an increased risk of conversion to clinical MS
within a mean follow-up of 3.5 years. Uhthoff's Symptom also correlates with a
higher incidence of recurrent optic neuritis.
1. the mode of onset and rate of progression of visual loss;
2. the location, character and severity of pain;
3. Symptoms that indicate involvement of structures adjacent to the optic nerve,
for example, the nasal sinuses, the olfactory nerve, the chiasm and/or the
pituitary gland; and
4. a complete symptomatic inquiry for previous disease of the eye and/or central
nervous System (CNS) for symptoms suggestive of demyelinating disease.
A medical history should include details of all medications,
particularly those that can produce optic nerve or retinal toxicity
(including ethambutol, isoniazid, phenothiazines and anti-neoplastic agents).
Drug and alcohol use, recent head and eye trauma (and the medico-legal details), as
well as stress and psychiatric disorder(s) must also be recorded.
The clinical signs of optic neuritis mirror those of optic
nerve disease. They are as follows:
• Visual acuity (distance and near) - reduced
• Dyschromatopsia
• Contrast sensitivity - impaired
• Stereo-acuity - reduced
• Visual field - generalized depression, central, paracentral and cecocentral scotoma
• Afferent pupillary defect
• Optic disc(s) - hyperemia and acute swelling.
Most patients with recovered optic neuritis and 20/20 Snellen acuity
insist that vision in the affected eye(s) is imperfect.
Using psychophysical tests, such as contrast sensitivity measurements,
investigators have been able to detect the hidden visual loss.
One important outcome of this research is that optic neuritis patients who have
difficulty seeing and 20/20 vision are protected from misdiagnosis as non-
organic cases of functional amblyopia. Low contrast letter wall charts
provide the clinician with an easy method for measuring contrast sensitivity.
Pelli-Robson low contrast letter charts discriminate normal from abnormal peak
contrast function (a mid-range spatial frequency), and provide reproducible
results [25]. The measurement of peak contrast sensitivity is an extremely effective
indicator of subclinical optic neuritis.
However, the test is not usefui in differentiating optic neuritis from
maculopathies, and because it is a subjective test, it is of no value in
distinguishing organic from non-organic factitious visual loss.
STEREO-ACUITY:
The Titmus polaroid 3-D vectograph Stereo-acuity test is recommended for both children and adults with optic neuritis. Individuals with normal 20/20 vision in each eye, and binocular fixation (no manifest strabismus), have an average stereopsis of 40 seconds of are. Stereo-acuity is reduced as acuity decreases down to 20/200, at which level monocular and binocular responses become identical. The value of a normal stereo-acuity in the presence of impaired Snellen acuity indicates either that the Snellen acuity is incorrect or that the patient is claiming poor acuity and the visual loss is factitious.
THE VISUAL FIELD:
(Großes JPG zum Geschichtsfeld)
In acute optic neuritis, the cardinal field defect is a widespread depression of
sensitivity, particularly pronounced centrally as a cecocentral scotoma.
An isolated central scotoma is atypical in demyelination; this pattern is more typical
of Leber's hereditary optic atrophy or of a toxic-nutntional optic neuropathy.
In unilateral cases of optic neuritis plotting the field of the contralateral eye
is particularly important since the detection of a subtle temporal depression may indicate
the presence of a sellar mass. A finding of generalized depression,
paracentral scotomas or scattered nerve fiber bundle defect(s) between
5 degrees and 20 degrees from fixation may indicate sequelae of prior demyelinating
optic neuropathy.
THE AFFERENT PUPILLARY DEFECT:
Unless there is an optic nerve lesion in the fellow eye from previously unrecognized
optic neuritis, a unilateral relative afferent pupil defect (RAPD) will be present in
the symptomatic neuritic eye.
Normal pupillary response consists of prompt, cymmetric constriction
(miosis) on exposure to light or on near convergence. Diminished response to a direct
light Stimulus, combined with a normal consensual pupillary response following
stimulation of the contralateral eye, characterize the RAPD.
The best way to elicit the RAPD is to perform a swinging flashhght test[26].
To perform this test the examiner should maintain a rhythmic equal time
alternation of the light from one eye to the other to avoid
asymmetric retinal bleach[27]. An afferent pupil defect can be assessed even if one
pupil is unreactive due to mydriatics, miotics, oculomotor
palsy or trauma. In such cases, when performing the swinging flashlight test,
the direct and consensual responses of the single reactive pupil must be compared.
The reactive pupil's direct light response reflects the afferent function of the
ipsilateral eye; its consensual response reflects the afferent function of the contralateral
eye. A unilateral afferent pupillary defect can be roughliy quantified by the use
of graded neutral density filters. By placing a neutral filter in front of the
normal eye, the examiner can effectively eliminate the relative afferent defect by
'balancing' the visual loss in the two eyes. The filter density needed to balance
the pupil defect is a measure of the loss of input to the affected eye and can be
compared to earlier measurements for evidence of Progression of the disease process.
In acute optic neuritis, the incidence of the RAPD is 44-76%. In recovered optic
neuritis, the incidence drops to 17-55% [6].
In the absence of a maculopathy, the RAPD is a highiy sensitive sign of an
ipsilateral optic nerve lesion and can be seen in an eye with 20/20 vision.
THE OPTIC DISC:
The appearance of the optic disc in acute optic neuritis is normal in 64%, swollen (papillitis) in 23%, blurred and/or hyperemic in 18% and blurred with peripapillary hemorrhages in 2%. Temporal pallor occurs in 10% suggesting a preceding attack of optic neuritis in the same eye. In recovered optic neuritis, 6 months after the first attack, a normal disc is present in 42% of eyes, temporal pallor in 28% and total disc pallor in 18%. In MS in remission, optic pallor is present in 38% of eyes.
THE RETINA:
Two retinal signs are associated with optic neuritis and MS:
retinal venous
sheathing due to periphlebitis retinae and defects in the retinal nerve fiber layer.
Retinal venous sheathing, characterized by deposits of a small, round or
ill-defined confluent white exudate along a peripheral vein usually associated with
vitreous cells, is present in 28% of patients wich isolated optic neuritis.
In a systematic study of 50 patients presenting with acute optic neuritis, retinal
vascular abnormalities and/or signs of inflammation were found in 14 patients:
fluorescein leakage in 10, perivenous sheathing in 6, cells in the vitreous in 6,
and in the anterior chamber in 4. In 2 patients, cells in the media were seen
without retinal changes. After a mean follow-up of 3.5 years, MS had developed in
8/14 patients with retinal vascular abnormalities and/or evidence of
inflammation and in 5/32 without these features.
The difference is significant.
Retinal venous sheathing in the MS eye occurs as an apparently
isolated asymptomatic condition, usually in both eyes.
The condition can resolve completely and then recur.
Some investigators have concluded that virtually all MS patients develop
venous sheathing at some point in their lifetime.
Others have reported an incidence of only 10 % in the MS population they studied,
and associate venous sheathing pre-eminently with progressive MS.
In this group of patients sheathing remained unchanged for periods varying from 5 to 11
months, with an extreme of up to 2 years. The connection between venous
sheathing and demyelination is important. The occurrence of perivenular
abnormalities in a region free of myelin and oligodendrocytes shows that
vascular changes in MS can occur independently of contiguous demyelination
and in fact may be the primary event in the formation of a new lesion.
The finding of retinal venous sheathing in a patient in whom a diagnosis of optic
neuritis or MS is suspected but not confirmed is of diagnostic
significance.
Atrophy of the nerve fiber layer precedes the appearance of obvious
optic atrophy and occurs in all types of optic neuropathy regardless of etiology.
In the MS eye, insidious atrophy of retinal nerve fibers occurs without
visual symptoms of optic nerve dysfunction. Defects in the retinal nerve fiber layer
due to axonal atrophy are seen in optic neuritis and MS as slits in the
nerve fiber striations in the arcuate fiber bundles. The incidence of retinal slits in
MS is as high as 70% and when slits are seen in the normal eye of a patient with
contralateral optic neuritis, they constitute evidence for a second subclinical
optic nerve lesion.
DIFFERENTIAL DIAGNOSIS:
Errors in the diagnosis of optic neuritis can be minimized if the neurologist is alert to discrepancies in the clinical picture presented. These include unusual features in the onset or course; for example, the absence of pain or onset over 50 years of age, failure to remit and or the presence of neurological abnormalities in the upper cranial nerves not attributable to MS.
Unilateral optic neuritis:
The differential diagnosis of unilateral optic neuritis includes ischemic optic neuropathy, rhinogenous optic neuritis from sinus disease, Lyme borreliosis optic neuropathy, Syphilis, HIV-associated optic neuropathies and non-organic factitious visual loss.
SIMULTANEOUS OR SEQUENTIAL BILATERAL OPTIC NEURITIS:
When optic neuritis strikes both eyes, simultaneously or sequentially, the disorder must be distinguished from Devic's disease, immune mediated optic neuropathy, nutritional amblyopia, Jamaican optic neuropathy, Leber's hereditary optic neuropathy and functional blindness. Devic's disease, neuromyelitis optica, is an inflammatory CNS demvelinating disease which is considered to be a variant of MS. Devic's affects both eyes simultaneously or sequentially in children, in young adults, and in the elderly, and is accompanied by transverse myelitis within days or weeks. The condition is rare in the US. An updated clinical profile of neuromyelitis optica and the prognostic implications of a single attack in two patients has recently been reported together with a review of 43 cases from the literature. The data show that the presenting symptom is bilateral optic neuritis in 36% of patients, unilateral optic neuritis in 40%, transverse myelitis in 13%, and simultaneous optic neuritis and transverse mvelitis in 11%. The interval between development of optic neuritis and transverse myelitis ranges from simultaneous onset to 7 weeks; in 60% of patients, the interval is less than one week. The severity of the optic neuritis tends to correlate with the severity of the transverse myelitis. In most patients the visual deficit is bilateral (91%) and usually severe, with unilateral or bilateral blindness in 58%. Eighty-four per cent of cases have an abnormal cerebrospinal fluid (CSF) during the acute stage of the illness: 62% of these cases have elevated CSF protein and 61% CSF pleocytosis. The reported neurological outcome indicates that 70% of the patients improve neurologically, 14% have a poor outcome and 16% die in the acute stage. Predictors of a poor outcome are older age, high CSF pleocytosis and severe myelitis. Forty-two per cent of patients have a recurrence of demyelinating disease after the initial recovery, consistent with a diagnosis of MS.
IMAGING PLAQUES:
Before the use of brain CT and MRI, the presence of CSF pleocytosis and
oligoclonal immunoglobulin provided paraclinical evidence of the dissemination of
lesions and met the criteria for the diagnosis of laboratory-supported
MS in isolated optic neuritis. They indicated an increased risk of progression to
MS. Brain and orbit CT scans are used to ehminate a compressive lesion or to
evaluate the nasal sinuses. In optic neuritis the CT can show transient enlargement
and contrast enhancement of the affected nerve. Brain MRI, with and without
gadolinium, is more sensitive than CT for imaging multifocal plaques in the
white matter. MRI abnormalities of this type occur in 56-72% of adult patients with
isolated optic neuritis and in 90-98% of patients with
climcally defimte MS. Modification of the brain imaging technique
using the STIR sequence (an inversion recovery sequence with a short inversion time)
and a surface coil specially designed for orbit imaging, increases the diagnostic
potential of visualizing piaques in the optic nerve(s). Using this technique
investigators examined 37 adult patients (25 women and 12 men) with known optic
neuritis [16]. Twenty-nine patients (78%) had isolated optic neuritis; 8 (21%)
had probable or definite MS. Focal high-signal MRI lesions were detected in 84% of
symptomatic and 20% of asymptomatic optic nerves. The mean
longitudinal extent of the lesions measured l centimeter.
Lesion sites were classified as:
(a) anterior, when the lesion was in continuity
with the nerve head and did not extend beyond midorbit;
(b) intraorbital,when it extended from midorbit to the optic canal;
(c) intracanalicular, when it was within the optic canal;
(d) intracranial, when that portion of the optic nerve
was involved; and
(e) chiasmal, when the chiasm was affected.
Lesions frequently struck more than one site in in 44 symptomatic optic nerves. The retrobulbar segment was most commonly involved, with an incidence of 61% in the mid-intraorbital region. No additional lesions were seen with gadohnium-enhanced MRI, although in one patient gadolinium demonstrated intracranial nerve and chiasmal involvement that was not visible with the STIR sequence.
PROGNOSIS:
VISUAL RECOVERY:
Although irreversible optic nerve damage occurs in 85% of optic neuritis patients,
the prognosis for the recovery of Snellen acuity is good:
65-80% of cases regain an acuity of 20/30 or better. Forty-five per cent of
these cases recover rapidly within the first four months; 35% recover normal
or near normal acuity at l year; and 20% fail to make any significant improvement.
In a multicenter study to evaluate visual recovery, following a trial of steroid
therapy - the optic neuritis treatment trial (ONTT) - visual function was assessed
after a 6- and 12-month follow-up period.
The three arms of the trial were:
1. intravenous (IV) methylprednisolone (MP) (Solumedrol
250mg every 6 hours) for 3 days followed byoral prednisone
(Deltasone l mg/kg body weight per day, rounded to the nearest 10mg) for 11 days;
2. an oral prednisone group (Deltasone l mg/kg body
weight per day) for 14 days; and
3. a placebo group.
Results showed that in the group receiving IV MP followed by oral prednisone visual function recovered faster than in the placebo group; this was particularly true for the reversal of visual field defects. However, IV MP followed by oral prednisone did not improve visual outcome after l year and the outcome in the oral prednisone group did not differ from that in the placebo group.
RECURRENT OPTIC NEURITIS:
In the author's patient population in New England, optic neuritis
recurred in 33% (33/101) of unilateral monosymptomatic optic neuritis patients
(36% women, 25% men) in one or the other eye during an 8-year
follow-up period. In 81 unselected patients with a first attack of acute
monosymptomatic optic neuritis, the incidence of recurrent attacks
was significantly greater in patients with Uhthoff's Symptom
(18 of40 or 47.5%) than in patients without Uhthoff's Symptom (4 of 41 or 10%).
The high incidence of recurrent optic neuritis in patients with Uhthoff's
Symptom is of prognostic value and accords with other published data.
In the ONTT 18 patients (13%) in the IV MP followed by oral prednisone group,
39 (30%) in the oral prednisone group, and 20 (16%) in the placebo
group had at least one new episode of optic neuritis in either eye during the
6-24 months of follow-up. Analysis of the length of time to the first new
episode of optic neuritis in either eye demonstrated that the rate of
new episodes was significantly higher in the oral prednisone
group (P = 0.02).
This was an unexpected finding that prompted the investigators, in
1993, to issue a warning to physicians that oral prednisone alone is
contraindicated in the treatment of optic neuritis !
CONVERSION TO MULTIPLE SCLEROSIS:
The probability that an individual with optic neuritis will develop MS
is high. Nearly half of the patients will convert to MS in 15 years.
At the lower end of risk, several studies suggest a conversion rate of
one-third to one-half and at the higher end, of 60%, 71% and even higher.
In the ONTT definite MS developed within the first 2 years in 8% (134 patients)
of the IV MP followed by prednisone group, in 16% (129 patients) of the oral
prednisone group and 18% (126 patients) of the placebo group.
CONCLUSION:
Progress in medicine is based on research. Research conclusions
ultimately rest on experimentation involving human subjects.
After decades of uncertainty, guidelines for the treatment
of the commonest herald svmptom of MS, optic neuritis, are now in place.
Patients who fit the ONTT profile of acute unilateral idiopathic
optic neuritis should now be informed of the association between
optic neuritis and MS, and a brain
MRI to establish the risk of conversion to clinical MS
should be performed. The MRI distinguishes two
groups of patients:
Klicken Sie hierhin oder
benutzen Sie die Back-Funktion Ihres Browsers, um zur EMD-Seite
zurückzukehren!
Howwever, the beneficial effect of the intravenous steroid regimen
appeared to lessen after the first two years of follow-up and by
the third year after treatment, the rate of developing definite MS
appeared similar in all treatment groups.
Brain MRI now provides the means to assess the risk of conversion to clinical MS.
In the ONTT abnormal scans with multifocal white matter
lesions were present in 46.9% of the patients and the MRI proved to be a
powerful predictor of MS.
Patients in the placebo group, with two or more periventricular white matter
lesions measuring at least 3mm in size had a 36% chance of
developing MS after two years; patients with one signal abnormality had a
17% chance of converting to MS; and those with no abnormality had only a
3% chance.
Intravenous MP followed by oral prednisone had its greatest impact on
delaying the early development of MS in patients whose MRI scans were most abnormal.
Among patients with two or more signal abnormalities,the two-year development of
MS was reduced from 36% to 16%; in those with one abnormality, from 17% to
11%. In those without signal abnormalities, the incidence of MS was so low (3%)
that the therapeutic efficacy could not be determined.
The delay in conversion to MS for up to 24 months after a single
3-day course of IV MP followed by oral prednisone is a highly
important observation. Prior to this report,
the only agents found to alter the natural history of the
relapsing-remitting (RR) form of MS were gamma Interferon which increased
the rate of new clinical attacks, and COP I and interferon beta-lb which reduced
the number of attacks. Critical points raised are:
first, that this study was only partially blinded and
patients assigned to the in-hospital IV MP followed by
prednisone therapy group knew that they had received high-dose MP, and
secondly, that although the statistical
analyses are thorough, the actual number of patients in
whom MS developed was small: 18 in the placebo group,
19 in the oral prednisone group and 10 in the IV MP
group.
Nevertheless, the statistical difference was larger
than typically seen in clinical trials, and it was found in
patients with a variety of demographic features and from
all 15 recruitment centers.
Group I - MRI normal, and Group
II - MRI positive, based on the presence of multifocal
periventricular white matter lesions consistent with
demyelinating disease.
A US/Canadian multicenter, randomized, double-blind, placebo-controlled
clinical trial will, over the next three years, take us further along the research road
helping us determine whether Biogen's recombinant human interferon beta product,
avonex (interferon beta-la) is beneficial in delaying the onset of clinically
definite MS in Group II subjects who have experienced a first attack of optic neuritis
and who are at high risk for MS based on the presence of multiple brain MRI
signal abnormalities. All patients to be enrolled in the study will initially
recelve IV MP followed by oral prednisone therapy, within 14 days of symptom onset.
Subjects with bilateral optic neuritis will be ineligible for study
participation, but other patients who have a monosymptomatic attack
affecting the spinal cord, brain stem or cerebellum will be eligible to take part.