Visual recovery following acute optic neuritis

Abstract. This study reports the prospective follow–up of a cohort of patients with acute optic neuritis examined with serial visual tests, visual evoked potentials (VEPs), conventional and triple–dose gadolinium (Gd)–enhanced magnetic resonance imaging (MRI) to examine which factors are important in visual recovery. Thirty–three patients were recruited with acute unilateral optic neuritis. A clinical and VEP assessment was performed on each. Optic nerve MRI was performed using fast spin echo (FSE) (on all) and triple-dose Gdenhanced T₁–weighted sequences (n = 28). Optic nerve lesion lengths were measured. Serial assessments were performed on 22 of the patients up to one–year. Serial Gd–enhanced optic nerve imaging was performed on 15 of the patients until enhancement ceased. The final 30–2 Humphrey visual field mean deviation (MD) was 2.55 dB higher in patients in the lowest quartile of initial Gd–enhanced lesion length compared with the other quartiles (p < 0.01) but recovery was not related to the duration of enhancement. The initial recovery of Humphrey MD was 4.60 dB units per day in patients with good eventual recoveries (MD > –6.0 dB) and 0.99 dB per day in poor-recovery patients (p = 0.02).Good–recovery patients had mean central field VEP amplitudes 2.29 µV higher during recovery than poor-recovery patients (p = 0.047). The results suggest that factors which are associated with a better prognosis are: having a short acute lesion on triple–dose gadolinium enhanced imaging, higher VEP amplitudes during recovery and a steep gradient of the initial improvement in vision.     

Long time echo STIR sequence magnetic resonance imaging of optic nerves in optic neuritis

Magnetic resonance images of optic nerves were obtained in 20 patients with acute optic neuritis (ON), and assessed by means of clinical, visual field and visual evoked potential evaluations; the imaging was repeated 1 year later. The results of the conventional Short Tau Inversion Recovery (STIR) sequence obtained using short time echo (STE-STIR: 22 msec) were compared with those of the long time echo sequence (LTE-STIR: 80 msec). The conventional STE-STIR sequence revealed lesions in 57.2% cases of acute ON and in 42.9% of the optic nerves affected by previous ON: the LTE-STIR sequence was diagnostic in 95.2% of acute ON cases and in 85% of patients with previous ON. The calculated length of the optic nerve lesions was significantly longer in the images obtained using the LTE-STIR sequence than in those obtained using conventional STE-STIR sequences.

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Sommario Si descrivono i risultati ottenuti con indagini di Risonanza Magnetica (RM) dei nervi ottici (eseguite all'esordio e 12 mesi dopo) in 20 pazienti affetti da Neurite Ottica (NO) acuta, valutata in funzione della sintomatologia clinica e delle alterazioni campimetriche e del potenziale evocato visivo.Sono state analizzate le immagini RM in Short Tau Inversion Recovery (STIR) mettendo a confronto i rilievi ottenuti con sequenza Short Time Echo (STE-STIR: 22 msec) rispetto a quelli ottenuti con Long Time Echo (LTE-STIR: 20 msec). Mentre con la convenzionale STE-STIR è stato possibile rilevare lesioni a carico dei nervi ottici nel 57.2% delle Neuriti Acute e nel 42.9% delle Neuriti Pregresse, la metodica LTE-STIR è risultata diagnostica nel 95.2% delle Neuriti Acute e nel 85% delle Neuriti Pregresse.Sia nelle NO acute che nelle pregresse, la lunghezza delle lesioni a carico dei nervi ottici sono risultate significativamente maggiori rispetto a quelle ottenute con la convenzionale metodica STE-STIR.

     

Continuing optic nerve atrophy following optic neuritis: a serial MRI study

To investigate optic neuritis as a model for atrophy in multiple sclerosis (MS) lesions we performed serial magnetic resonance imaging (MRI) on 10 patients with a history of optic neuritis using a fat saturated short-echo fast fluid-attenuated inversion recovery (sTE fFLAIR) sequence. The first study was performed a median of 19.5 months after the onset of optic neuritis and the second 1 year later. Using a computer-assisted contouring technique, a blinded observer calculated the mean area of the intro-orbital optic nerves. The mean area of affected optic nerves decreased over 1 year by 0.9 mm2 from 11.1 to 10.2 mm2 (p = 0.01). Poor visual acuity and decreased visual-evoked potential (VEP) amplitude were associated with atrophy. These findings suggest that atrophy is a feature of focal demyelinating lesions, it may evolve over several years, and may have functional significance. Optic neuritis provides a model to study the effect of inflammatory demyelination through the ability to accurately measure visual function and to visualize and measure the optic nerves using magnetic resonance imaging.     

MRI, VEP, SEP and biothesiometry suggest monosymptomatic acute optic neuritis to be a first manifestation of multiple sclerosis

A cohort of 50 consecutive patients with acute monosymptomatic optic neuritis (ON) from a defined catchment area joined a prospective study. The aim of this study was to compare the sensitivity of magnetic resonance imaging (MRI), electrophysiological methods (VEP and SEP) and biothesiometry to detect abnormalities in other parts of the CNS than the optic nerves during the acute phase of ON. For each method, a scoring system is proposed. This investigation also hoped to achieve a better understanding of the natural history of ON. MRI proved to be the most sensitive tool (63% abnormal) in confirming a second site of involvement, followed by VEP in the clinically unaffected fellow eye (42%), biothesiometry (32%) and SEP (17%). The combination of all these methods, except for MRI (and VEP in eyes with acute ON), revealed abnormalities in 63% of the patients. When the neurophysiological methods were combined with MRI, 79% of the patients had abnormal findings suggesting additional lesions in the CNS. Hence, MRI and neurophysiological examinations supplement each other and together provide evidence that monosymptomatic ON is usually a first manifestation of MS. The development of definite MS at 1-20 months of follow up in 7 patients (all with abnormal MRI initially) supports this view.     

Dissecting structure–function interactions in acute optic neuritis to investigate neuroplasticity

Structural MRI, electrophysiology, and functional MRI (fMRI) elucidate different aspects of damage and repair in demyelinating diseases. We combined them to investigate why patients with optic neuritis (ON) exhibit a wide variation in severity of acute visual loss, with the following objectives: (1) To determine how structural and electrophysiological changes in the anterior and posterior visual pathways contribute to acute visual loss. (2) To combine these data with fMRI, to investigate whether cortical activity modulates visual acuity. The visual system of 28 patients with acute unilateral ON was assessed. Linear regression modeling was used to identify parameters associated with acute visual loss, and to determine whether fMRI activity was associated with vision, after accounting for structural and electrophysiological predictors, age, and gender. Optic nerve lesion length and visual evoked potential (VEP) amplitude were associated with visual loss. Bilateral activation in the extra‐striate occipital cortex correlated directly with vision, after adjusting for optic nerve lesion length, VEP amplitude, and demographic characteristics. These data suggest that acute visual loss is associated with the extent of inflammation and conduction block in the optic nerve, but not with pathology in the optic radiations or occipital cortex. The association of better vision with greater fMRI responses, after accounting for factors which reduce afferent input, suggests a role for adaptive neuroplasticity within the association cortex of the dorsal stream of higher visual processing. Longitudinal studies will clarify whether different extra‐striate cortical regions play a role in adaptive plasticity in the acute and chronic stages of injury. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Visual evoked potential is superior to triple dose magnetic resonance imaging in the diagnosis of optic nerve involvement

The aim of this study was to evaluate whether VEP is sensitive to optic neuritis (ON) when compared with triple dose orbital MRI. Twenty-four relapsing-remitting MS (RRMS) patients were included in the study. Group I (n = 10) patients with acute ON, Group II (n = 8): patients presenting with a current relapse who had the history of ON in the previous relapses. Group III (n = 6): patients presenting with a current relapse but with no history of ON. Neuro-ophtalmological evaluation. VEP investigation and orbital MRI with triple dose (0.3 mmol/kg) gadolinium (Gd) were carried out for all. VEP was found to be 70% sensitive and 12.5% specific to the acute ON, whereas orbital MRI with triple dose Gd was 70% sensitive and 100% specific. In chronic ON, the sensitivity of orbital MRI is 0%, whereas the VEP is still 75% sensitive to chronic optic nerve involvement and can distinguish the pathology 100% specifically. In conclusion, orbital MRI with triple dose Gd is not more sensitive than VEP in determining the acute optic nerve pathologies but it is a 100% specific method. The results suggest that VEP is superior to the orbital MRI in determining the chronic optic nerve involvement.     

Magnetic resonance imaging in optic nerve lesions with multiple sclerosis

Magnetic resonance imaging (MRI) of the optic nerves was performed in 10 patients with multiple sclerosis (MS) using short inversion time inversion recovery (STIR) pulse sequences, and the results were compared with the visual evoked potentials (VEP). The 10 patients had optic neuritis in the chronic or remitting phase together with additional symptoms or signs allowing a diagnosis of clinically definite or probable MS. Sixteen optic nerves were clinically affected and 4 were unaffected. MRI was performed using a 0.5 tesla superconducting unit, and multiple continuous 5 mm coronal and axial STIR images were obtained. A lesion was judged to be present if a focal or diffuse area of increased signal intensity was detected in the optic nerve. In VEP, a delay in peak latency or no P 100 component was judged to be abnormal. With regard to the clinically affected optic nerves, MRI revealed a region of increased signal intensity in 14/16 (88%) and the VEP was abnormal in 16/16 (100%). In the clinically unaffected optic nerves, MRI revealed an increased signal intensity in 2/4 (50%). One of these nerves had an abnormal VEP and the other had a VEP latency at the upper limit of normal. The VEP was abnormal in 1/4 (25%). In the clinically affected optic nerves, the degree of loss of visual acuity was not associated with the longitudinal extent of the lesions shown by MRI. The mean length was 17.5 mm in optic nerves with a slight disturbance of visual acuity and 15.0 mm in nerves with severe visual loss.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional Magnetic Resonance Imaging in Acute Unilateral Optic Neuritis

Despite good clinical criteria for diagnosing optic neuritis (ON), only a few techniques can precisely assess its impact on visual brain function. The authors studied whether functional magnetic resonance imaging (fMRI) of visual activation reliably reflects the cerebral consequences of acute unilateral ON, and how fMRI correlates with clinical function and visual evoked potentials (VEPs). Twenty ON patients, before and after steroid treatment, were compared to 20 controls. Each eye was stimulated separately with a checkerboard pattern reversing at 1, 2, 4, and 8 Hz. VEPs were recorded the same day. Initially, affected eye responses differed significantly from those of unaffected counterparts and controls in 12 patients. Post hoc classification by fMRI criteria was correct in approximately 85%. fMRI and VEP response parameters (as well as visual acuity) correlated significantly. The higher stimulation frequencies yielded greater fMRI responses from unaffected eyes, but not from affected eyes, in controls. The fMRI responses were quantifiable in every subject, whereas in 11 ON eyes, no VEPs were obtained during the acute stage. The authors conclude that fMRI is sensitive to the cerebral response alteration during ON and might therefore contribute to evaluating the temporal evolution of the visual functional deficit during recovery or therapy.     

Multifocal visual evoked potentials in optic neuritis and multiple sclerosis: A review

Multifocal visual evoked potential (mf-VEP) represents a new approach to the classical full field (ff-)VEP with separate responses from up to 60 sectors of the visual field. A thorough literature survey of the use of mf-VEP in optic neuritis (ON) and multiple sclerosis (MS) is presented (38 published studies were retrieved). Mf-VEP provides direct topographical information of specific lesions and facilitates investigations on structural-functional correlations thus providing new methods for exploring the interplay between demyelination, atrophy and remyelination in MS. Good correlation was shown between mf-VEP and OCT, ff-VEP, MRI (MTR, DTI), 30-2 standard automated perimetry and low-contrast-visual acuity. All but one study showed superior sensitivity and specificity compared to ff-VEP, especially with regards to small, peripheral lesions or lesions of the upper visual field. Mf-VEP has shown superior sensitivity and specificity than established methods in diagnosing optic nerve lesions and tracking functional recovery following lesions. Abnormal mf-VEP responses in the fellow, non-ON afflicted eye may predict MS risk in ON patients. No standardization currently exists and no direct comparisons in ON and MS between at least 5 different commercially available mf-VEP systems have so far been published. Despite these limitations, mf-VEP is a promising new tool of diagnostic and prognostic value of mf-VEP in ON and MS.     

Recovery from optic neuritis is associated with a change in the distribution of cerebral response to visual stimulation: a functional magnetic resonance imaging study

OBJECTIVES: Recovery to normal or near normal visual acuity is usual after acute demyelinating optic neuritis, despite the frequent persistence of conduction abnormalities as evidenced by the visual evoked potential (VEP). This raises the possibility that cortical adaptation to a persistently abnormal input contributes to the recovery process. The objective of this study was to investigate the pattern of cerebral response to a simple visual stimulus in recovered patients in comparison to normal subjects. METHODS: Functional magnetic resonance imaging (fMRI) was used to study the brain activation pattern induced by a periodic monocular 8Hz photic stimulus in seven patients who had recovered from a single episode of acute unilateral optic neuritis, and in seven normal controls. VEPs and structural optic nerve MRI were performed on patients. RESULTS: Stimulation of either eye in controls activated only the occipital visual cortex. However, in patients, stimulation of the recovered eye also induced extensive activation in other areas including the insula-claustrum, lateral temporal and posterior parietal cortices, and thalamus; stimulation of the clinically unaffected eye activated visual cortex and right insula-claustrum only. The volume of extraoccipital activation in patients was strongly correlated with VEP latency (r = 0.71, p = 0.005). CONCLUSIONS: The extraoccipital areas that were activated in patients all have extensive visual connections, and some have been proposed as sites of multimodal sensory integration. The results indicate a functional reorganisation of the cerebral response to simple visual stimuli after optic neuritis that may represent an adaptive response to a persistently abnormal input. Whether this is a necessary part of the recovery process remains to be determined.     

Optic nerve magnetization transfer imaging and measures of axonal loss and demyelination in optic neuritis

Magnetization transfer imaging is an MRI technique that provides quantitative information about in vivo tissue integrity, including myelin and axonal content, and is expressed as the magnetization transfer ratio (MTR). The optic neuritis lesion can model the MS lesion in vivo and permits use of non-invasive markers of optic nerve myelination (visual evoked potential [VEP] latency) and retinal neuroaxonal loss (optical coherence tomography [OCT]) to provide further information about the in vivo substrates of optic nerve MTR. Twenty-five patients with optic neuritis were studied using an optic nerve MTR sequence, quantitative visual function testing, VEPs and OCT, along with 15 controls. MTR was reduced in affected nerves compared to both clinically unaffected nerves from patients and control nerves (P < 0.001). Whole-nerve MTR correlated modestly with central-field VEP latency but more strongly when lesion-only MTR was measured, when a modest correlation with whole-field VEP latency emerged. OCT-quantified retinal neuroaxonal loss also correlated with MTR. In conclusion, markers of optic nerve myelination and axonal loss both correlate with optic nerve MTR. Because axonal loss following optic neuritis also results in myelin loss, the relative contributions of the two pathological conditions to the MTR measures cannot be estimated from this study.     

Magnetic resonance imaging of the optic nerve in optic neuritis

Magnetic resonance imaging (MRI) of the optic nerves using the STIR (short inversion time inversion recovery) sequence was performed in 37 adult patients with a recent or past attack of optic neuritis. MRI revealed high-signal regions in 84% of symptomatic and 20% of asymptomatic nerves. The mean longitudinal extent of lesions was 1 cm. Slow or poor visual recovery was associated with more extensive lesions, or lesions within the optic canal. Disk swelling was usually associated with anterior lesions but also occurred with lesions in the canal. Visual evoked potentials were even more sensitive than MRI in detecting lesions and are still the investigation of choice in suspected demyelinating disease involving the optic nerve.     

Neurophysiological and CSF immunological study of 19 patients affected by acute idiopatic optic neuritis

We studied 19 patients affected by acute idiopatic optic neuritis (ON), with neurophysiological tests: visual (VEP), somatosensory (SSEP), acoustic (ABR) evoked potentials and study of the blink reflex (BR), and with cerebrospinal fluid (CSF) examination, in order to detect "silent" lesions in the central nervous system (CNS) and/or immunological alterations, suggestive of multiple sclerosis (MS). The percentage of cases with at least one altered CSF IgG parameter (IgG index, IgG synthesis/day and IgG oligoclonal bands) has been higher than that of cases with one or more altered neurophysiological tests, regardless of the apparently intact eye VEP. If we also included this last test, the 2 percentages become identical. The validity of these tests in predicting the evolution of ON in MS is discussed.     

Do visual evoked potentials give relevant information to the neuro-ophthalmological examination in optic nerve lesions?

The visual evoked potentials (VEPs) and neuro-ophthalmological examinations of 134 patients were compared. The VEPs were abnormal in 95 % of the eyes with optic neuritis. Defective color vision was found in 99 %, visual field defects in 88 %, decreased vision in 66 % and an afferent pupillary defect in 55 %. 29 patients with optic neuritis were followed up with repeated tests. VEPs and color vision recovered more slowly than visual acuity and visual field.
Abnormal VEPs were observed in 68 % of 50 MS patients. An analysis of symptomatic and asymptomatic eyes showed that testing of color vision, visual field and red-free ophthalmoscopy were equally as useful diagnostic tools as VEPs. 4 (8 %) of the MS patients had abnormal VEPs despite a normal neuro-ophthalmological examination; 94 % of MS patients with symptoms and 47 % of MS patients without visual symptoms had abnormal VEPs.
VEPs were pathological in 59 % of 24 patients with traumatic or compressive optic nerve diseases or optic atrophies of unknown etiology. The neuro-ophthalmological examination was more sensitive than VEPs in the diagnosis of these disorders. A neuro-ophthalmological examination is in most cases sufficient to diagnose optic nerve lesions. VEPs are of diagnostic aid especially in mild optic nerve lesions.     

Variation of visual evoked potential delay to stimulation of central, nasal, and temporal regions of the macula in optic neuritis

OBJECTIVES: To compare the degree of visual evoked potential (VEP) delay to stimulation of central, nasal, and temporal regions of the macula in optic neuritis, to determine whether the differential involvement of parvocellular and magnocellular fibre types suggested by other studies is governed by retinotopic factors. METHODS: VEPs were recorded to reversal of 40' checks in the central (4 degrees radius) and the left and right surrounding regions of the visual field (as far as 10 degrees vertical and 14 degrees horizontal) in 30 patients recently recovered from the acute stage of optic neuritis, and in 17 age matched controls. RESULTS: In the control group, VEP latencies were similar to stimulation of the central and temporal regions of the macula, marginally shorter from the nasal region. In the patients with optic neuritis, VEPs were significantly more delayed from the central region, on average by about twice as much as from the nasal and temporal regions. Delays seen in some of the VEPs from the patients' fellow eyes tended to be more uniformly distributed. CONCLUSIONS: Although the central region of the macula is where the density of parvocellular innervation is greatest, there is no reason to suppose that the VEPs to stimulation of the nasal and temporal regions (almost all P100 activity arising from within the central 10 degrees ) are mediated by fibres of another type. Consequently it is suggested that the central fibres were most affected by demyelination, not on account of their belonging to the parvocellular type but because of their particular situation in the optic nerve. Centrally located fibres may experience greater exposure to factors causing demyelination, or fibres located closer to the edge of the plaque may undergo more effective remyelination in the first few weeks after the acute episode.     

VISUAL EVOKED POTENTIAL IS SUPERIOR TO TRIPLE DOSE MAGNETIC RESONANCE IMAGING IN THE DIAGNOSIS OF OPTIC NERVE INVOLVEMENT

The aim of this study was to evaluate whether VEP is sensitive to optic neuritis (ON) when compared with triple dose orbital MRI. Twenty-four relapsing-remitting MS (RRMS) patients were included in the study. Group I (n = 10) patients with acute ON, Group II (n = 8): patients presenting with a current relapse who had the history of ON in the previous relapses. Group III (n = 6): patients presenting with a current relapse but with no history of ON. Neuro-ophtalmological evaluation. VEP investigation and orbital MRI with triple dose (0.3 mmol/kg) gadolinium (Gd) were carried out for all. VEP was found to be 70% sensitive and 12.5% specific to the acute ON, whereas orbital MRI with triple dose Gd was 70% sensitive and 100% specific. In chronic ON, the sensitivity of orbital MRI is 0%, whereas the VEP is still 75% sensitive to chronic optic nerve involvement and can distinguish the pathology 100% specifically. In conclusion, orbital MRI with triple dose Gd is not more sensitive than VEP in determining the acute optic nerve pathologies but it is a 100% specific method. The results suggest that VEP is superior to the orbital MRI in determining the chronic optic nerve involvement.     

The natural history of optic neuritis

Optic neuritis is a common cause of visual loss in young patients, typically presenting with painful monocular visual loss and decreased color vision. Visual function generally spontaneously improves over weeks, and 95% of patients return to visual acuity of at least 20/40 within 12 months. The initial magnetic resonance imaging (MRI) helps stratify the risk of multiple sclerosis (MS) in patients with acute isolated optic neuritis. In the Optic Neuritis Treatment Trial, the 10-year risk of MS in the group of patients with at least one MRI T2 lesion was 56%, whereas the 10-year risk with a normal baseline MRI was 22%. A normal MRI in concert with painless optic neuritis, severe optic nerve head edema, peripapillary hemorrhages, or a macular star defines a very low MS risk subgroup. High-dose steroids hasten the rate, but not the final extent, of visual recovery in optic neuritis, and the decision to use this therapy is individualized. Interferon beta-1a therapy should be considered in selected high-risk patients.     

A longitudinal conventional and magnetization transfer magnetic resonance imaging study of optic neuritis

Eleven consecutive patients with a first episode of acute optic neuritis were evaluated, using conventional and magnetization transfer (MT) magnetic resonance imaging (MRI), in order to assess the temporal evolution of optic nerve (ON) damage and to investigate the correlation of ON damage with visual outcome and electrophysiological parameters. Patients underwent neuroophthalmological, neurological, electrophysiological, and MRI assessments at baseline and after three and 12 months. ON volumes were measured on coronal T1-weighted images using a local thresholding segmentation technique. MT ratio (MTR) from the ON was derived from gradient echo images. No significant volume difference was detected between affected and healthy ON, both at baseline and follow-up. At baseline, mean MTR values were significantly higher in affected ON than in healthy ON (P =0.001), whereas at months 3 and 12, the mean MTR values were significantly reduced in the affected ON (P =0.02 and 0.003, respectively). Mean MTR of the affected ON, corrected for healthy ON values, progressively decreased over time (P =0.04 at month 3 and P =0.0012 at month 12). On the contrary, MTR values of healthy ON remained stable. No correlations were found between MTR measures and clinical or electrophysiological data. This study shows the presence of subtle pathological changes, possibly due to residual demyelination and subsequent additional demyelination and impaired remyelination, in the ON of patients with a first episode of optic neuritis. In the early phase of optic neuritis, MT MRI is more sensitive than atrophy measurements in detecting disease-related changes.     

Acute optic neuritis: clinical and MRI prognostic factors. Study of fifty patients

The objective of this study was to evaluate the risk of visual outcome after acute optic neuritis (ON) in relation to clinical and MRI findings. Fifty cases of acute ON within one month were retrospectively studied. MRI with Short Tau Inversion Recovery (STIR) sequence of the optic nerve were obtained with a median time onset of 9 days after ON. Mean age of patients was 32.8 years, mean initial visual acuity was 3/10 and orbital pain was present in 86 percent100 of patients. The STIR sequence revealed lesion in 88 percent 100 of acutely symptomatic optic nerves. An initial low visual acuity (less than 2/10), the absence of orbital pain and involvement of the intracanalicular portion of the optic nerve on STIR sequence were statistically correlated with a poorer visual outcome (respectively p=0.0041, p=0.035 and p=0.011).