Serial cases: visual evoked potentials (VEP) in demyelinating disease

Objective To observe the clinical features and visual function of recurrent neuromyelitis optica (NMO).Methods Thirty-four patients with NMO were enrolled in this retrospective case series study.The patients included two males and 32 females.The average first onset age was (35.03± 14.56) years old and the average recurrent rate were (4.24±2.45) times.The recurrent rate of optic neuritis (ON) ranged from two to 12 times.The recurrent rate of ON was two times in 15 eyes of 10 patients,≥three times in 37 eyes of 24 patients.Vision acuity,direct ophthalmoscope,fundus pre-set lens examination,visual field and visual evoked potential (VEP) were evaluated.Clinical features were observed.The abnormal rate of optic nerve including optic edema and atrophy; abnormal rate of visual field including decreasing retinal sensitivity,central and paracentral scotoma,ring scotoma,half field defects,tunnel visual field,visual field centrality constriction; abnormal rate of VEP including Prolonged latent phase and/or decreasing amplitude of P100 wave from patients of first episode or recurrence was analyzed.Serum NMO-IgG was detected from 28 patients hy indirect immunofluorescence technique to observe its positive rate.Results All patients were characterized by repeated episodes of ON and myelitis.The main clinical feature of ON was visual loss,and the main clinical features of myelitis included sensory disability,dyskinesia and vesicorectal disorder.Blindness rate was 41.67％ after the first attack of ON,33.33％ after two relapses,and 64.86％ after ≥ three relapses.The difference of blindness rate between first attack and two episodes was not significant (x2=0.270,P=0.603).However,the blindness rate in patients having ≥ three episodes was significantly higher than those having two episodes (x2=4.300,P=0.038).With recurrence rate increasing,the abnormal rate of the optic nerve (x2 =6.750,P =0.034) and VEP(x2 =6.990,P =0.030)increased.But the abnormal rate of visual field did not increase along with recurrent rate (x2 =0.660,P=0.718).Seropositive rate of NMO-IgG did not differ significantly between patients with first attack ON and that with recurrent ON (x2 =1.510,P =0.470).But the seropositive patients had significantly higher bilateral blindness rate than seronegative patients (x2=5.063,P=0.027).Conclusions NMO are characterized by recurrent ON and myelitis.Visual loss,sensory disability,dyskinesia and vesicorectal disorder are the main clinical features.With recurrence rate increasing,the blindness rate,abnormalities the optic nerve and the abnormity rate of VEP increase.Seropositive recurrent NMO patients have higher bilateral blindness rate than seronegative patients. Key words: Neuromyelitis optica/diagnosis; Optic neuritis/diagnosis; Vision, binocular; Vision,low; Visual fields

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

2. Visual evoked potentials in the diagnosis of multiple sclerosis

Background: The aim was to compare the retinal nerve fibre layer (RNFL) thickness and visual evoked potentials (VEP) among eyes with multiple sclerosis (MS)‐associated optic neuritis, unaffected eyes of the same patients and eyes of disease‐free controls. Changes in RNFL thickness, visual acuity (VA) and VEP over time are evaluated in MS‐associated optic neuritis.Methods: Forty‐six eyes of 23 patients (six male and 17 female), who suffer from MS and were diagnosed with unilateral or bilateral optic neuritis, participated in the study. Forty eyes of 20 age‐ and gender‐matched controls were tested. VA measurement, optical coherence tomography and VEP were performed in all patients at presentation and at one, three and six months thereafter.Results: There was a statistically significant difference in VA between MS eyes with optic neuritis and controls (p < 0.0001), as well as between MS eyes with and without optic neuritis (p < 0.005). VA improved over time. Average RNFL thickness was reduced in MS eyes with or without optic neuritis in comparison to control eyes. This reduction in RNFL thickness was more marked over time. The amplitude of P100 was significantly decreased in MS eyes with optic neuritis in comparison to controls (p < 0.0001) and there was a statistically significant delay in peak time of P100 in MS eyes with optic neuritis versus the eyes of normal subjects (p < 0.0001), which improved over time.Conclusion: The present study suggests that there is a progressive decrease in RNFL over time in eyes with optic neuritis associated with MS. The amplitude and latency of P100 in VEP examination returned to normal ranges over time.

Background: The visual evoked potential (VEP) is used in the evaluation of multiple sclerosis (MS) patients, showing a delay in P100 wave latency with no changes in amplitude in 60–100% of cases. In the last decade, the recurrent form of neuromyelitis optica (NMO) has been recognized, and clinically characterized by acute events of transverse myelitis (TM) and optic neuritis (ON), differing from MS in clinical and laboratory criteria. Despite these differences, so far, the VEP parameters described in MS have been used in the evaluation of patients with NMO. The objective of this study was to investigate VEP responses in NMO. Methods: Patients with NMO underwent pattern-reversal visual stimulation. Nineteen patients were selected for the study. Results: Among the 38 eyes examined, 18 (47.4%) had no visual evoked responses and 13 (34.2%) had a reduction of P100 wave amplitude with normal latency. Only two (5.3%) had the pattern described in MS and five (13.2%) were normal. Conclusion: Evaluation of VEP in patients with definite NMO revealed a pattern that is different from that of MS in 81.6% of eyes examined, characterized by the absence of responses, or decreased amplitude with normal latency.

Optic neuritis (ON) is linked to multiple sclerosis (MS). The presence of white matter lesions on cerebral magnetic resonance imaging (MRI) predicts the risk of MS after ON with considerable accuracy. Oligoclonal bands (OCB) are present in 95 % of MS patients, and a lumbar puncture can also be valuable in the evaluation of patients with ON. We analyzed CSF findings in patients referred with ON in the context of MRI and visual evoked potential (VEP) pathology. We assessed the possible contributory role of a lumbar puncture and weigh this against disadvantages of the procedure. Between February 2003 and November 2011, 505 patients were referred by ophthalmologists to the Clinic of Optic Neuritis, Glostrup Hospital, University of Copenhagen. None had MS prior to referral. A total of 437 were included in the study, and all underwent MRI, a lumbar puncture and VEP. Patients with other organic causes of their symptoms and patients with >3 months between onset and tests were excluded. All files were reviewed retrospectively. CSF leukocytes and the IgG index were elevated in 33 and 41 %, respectively, and OCBs were detected in 61 % of patients. CSF abnormalities correlated strongly with VEP and MRI (p < 0.0001). Patients with normal VEP and MRI had a 96 % probability of a normal lumbar puncture. The contributory role of a lumbar puncture in the evaluation of ON seems negligible when patients have a normal VEP and MRI. We suggest that all patients should be evaluated with VEP and MRI before deciding on a lumbar puncture.

Nonenhanced T 1 -w sequences such as magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) and derived fluid and white matter suppression (FLAWS) have demonstrated high performance for detecting brain parenchymal and cervical spine demyelinating lesions in multiple sclerosis. However, their potential for identifying optic nerve (ON) demyelination remains unexplored. The aim of this study was to evaluate the performance of compressed sensing-accelerated (CS) MP2RAGE-FLAWS imaging for detection of ON demyelination lesions compared with T2-w fat-saturated (FS) TSE imaging in a clinical setting. We conducted a retrospective study of magnetic resonance scans acquired on patients with central nervous system demyelinating disorders between January and December 2022. Inclusion criteria were the acquisition in the same session of a brain CS-MP2RAGE-FLAWS imaging and a combination of axial + coronal T2-w FS orbital sequences. A 4-step radiological analysis-including blinded and consensus readings-assessed ON lesion detection. The reference standard was the final reading session of radiologists using the entire patient file. Sensitivities and specificities of both sequences were computed and compared using McNemar χ 2 tests. Thirty-nine patients (mean age: 43 ± 14 years; 25 women) were analyzed, including 34 with multiple sclerosis, 2 with MOGAD (myelin oligodendrocyte glycoprotein antibody-associated disease), 1 with NMOSD (neuromyelitis optica spectrum disorder), and 2 with indeterminate demyelinating disease. Among the 78 ONs analyzed, 64 lesions were detected with CS-MP2RAGE-FLAWS as opposed to 37 with 2D T2-w FS imaging, corresponding to a total of 41 and 27 affected nerves, respectively. CS-MP2RAGE-FLAWS exhibited higher sensitivity for overall detection of ON lesions compared with 2D T2-w FS imaging (97.5% vs 67.5%, P = 0.001) without reducing the specificity. Improved lesion detectability with CS-MP2RAGE-FLAWS was significant compared with 2D T2-w FS in intraorbital and intracanalicular segments (respectively, 92.3% vs 50% and 96.3% vs 66.7%; P < 0.05). There was no difference in sensitivity ( P = 0.69) or specificity ( P = 0.99) regarding the intracranial segment analysis. CS-MP2RAGE-FLAWS sequence improves ON lesion detection compared with conventional 2D T2-w FS, especially in the intraorbital segment, while simultaneously providing whole-brain and cervical spinal cord imaging at no additional time cost.

To compare the retinal layer thickness of eyes with optic neuritis (ON) and that of control eyes and ON eyes with and without neuromyelitis optica (NMO) or multiple sclerosis (MS). Horizontal and vertical SD-OCT scans of the fovea were undertaken for 56 patients with ON with and without NMO or MS and for 24 healthy controls. Patients with ON were divided into three groups: NMO, MS and isolated ON without NMO or MS. The thickness of each retinal layer was compared between ON and healthy control eyes, and between ON eyes with and without NMO or MS. Compared with healthy control eyes, ON eyes showed significant thinning of the ganglion cell layer plus the inner plexiform layer (GCL + IPL) at all eight inner and outer macular locations. Significant differences in thickness were observed for the retinal layers of NMO, MS and isolated ON without NMO or MS at several retinal locations. Our SD-OCT data revealed a notable difference in the GCL + IPL thickness between ON and healthy control eyes. It also showed differences in the thickness of several retinal layers for ON subgroups including NMO, MS and isolated ON. This may be helpful for distinguishing the aetiology of ON.

Interferon beta-1b exacerbates multiple sclerosis with severe optic nerve and spinal cord demyelination

Background Optic neuritis is closely associated with multiple sclerosis (MS).Its pathogenesis is uncompletely clear,and less basic researches are carried out at home and abroad. Objective This study was to reveal the expression of myelin basic protein (MBP) in the optic nerve of rat with experimental allergic encephalomyelitis (EAE) and to provide a theoretical evidence for the research of the relationship of optic neuritis with MS. Methods Fifty clean Wistar rats were randomized into the control group and immune 8,12,18 and 25 days groups.Myelencephalon was collected from 5 guinea pigs to prepare the homogenate and mixed with the isovolumetric complete Freud' s adjuvant (CFA).The 0.5 ml mixed antigen emulsifier was subcutancously injected into the 4 maps together with Bordetella pertussis 0.2 ml under the cutancous of dorsalis pedis at 0 and 48 hours to induce the EAE.Behavior of the rats was evaluated to score the neurological function.The optical nerve sections were prepared 8,12,18 and 25 days after immunology for the histopathological examination,and immunochemistry and Western blot were used to detect the expression of MBP in optic nerve.The use of the animals complied with the Regulation for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission. Results The disorder of motor nerve was seen 12 days following the immune,and the clinical neural functional scores were significantly higher 12 day and peaked on 18 days myelination and then gradually reduced.The histopathological examination showed that the irregular alignment of neural fiber was found at 12 days,and changes of cellular structure,edema of neural shaft bunch were observed at 18 days.However,the abnormal cells were significantly less 25 days following the immune.Immunochemistry showed that the MBP was expressed mainly in the myelination of optic nerve fibers.The numbers of positive cells for MBP were (115.75±26.49)cells/5 fields at the 12th day,showing a significant lowing in comparison with (167.44±22.49)cells/5 fields of control group (t=4.537,P＜0.05 ).The positive cells were lest at the 18th day with the values ( 75.57 ± 34.54) cells/5 fields ( t =6.362,P＜0.01 ).At the 25th day,positive cells increased to ( 117.63 ± 13.78) cells/5 fields,which still was lower than those of the control group ( t =4.068,P＜0.05 ).Western blot assay illuminated that with the prolong of immune time,MBP/β-actin ratio in optic nerve was gradually reduced and followed the same pattern at the 12th day( t =4.639,P＜0.05 ).At 18 days after immune in comparison with the control group,the expression of MBP/β-actin ratio in optic nerve was the least (t=8.427,P＜0.01). Conclusions MBP can be degraded in rat optic nerve.This is a further evidence that optic neuritis is a severe demyelination disease.It is clearly related to MS. Key words: Experimental allergic encephalomyelitis; Myelin basic protein; Multiple sclerosis; Optic neuritis

Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO), Fort Lauderdale, Florida, May 5-10, 2002.

Optic nerve atrophy and retinal nerve fibre layer thinning following optic neuritis: Evidence that axonal loss is a substrate of MRI-detected atrophy

Longitudinally extensive optic neuritis as an MRI biomarker distinguishes neuromyelitis optica from multiple sclerosis

Purpose: to compare subtle changes in retinal and optic disk morphology and microcirculation and the functional activity of visual channels in patients with multiple sclerosis (MS) and optical neuritis (ON) in the medical history. Material and methods: 19 patients with remitting MS (duration of about four years) and ON developed about six months ago were tested by standard neurologic and ophthalmologic techniques, optical coherent tomography (OCT) with the angio OCT (RTVue XR 100 Avanti) protocol. The pattern ERG (PERG), as well as visual evoked potentials (VEP), on the reversing black/ white, pure luminance (black/yellow) and chromatic (red/green and blue/yellow) chess stimuli were recorded (RETI-port/ scan, Roland Consult, Germany). Results: At the level of superficial capillary plexus, the density and the area of vessels were reduced in the parafoveal zone, and the blood flow index dropped significantly (to 82.6% against the control). No statistically significant changes of blood flow were found in the peripapillary zone. The peak latency of P50 in the PERG responses to all stimuli showed a statistically significant reduction. The peak latency of N95 was delayed by an average of 10 % as compared to the controls. The amplitude of PERG N95 was moderately reduced for stimuli of all sizes. The elongation of the culmination time for the peak P100 was shown to be significant only in the VEP responses to blue/yellow patterns with angular sizes of 16° and 0.3°. A decrease in the thickness of the ganglion cells (GCC) complex correlated highly with reduced microcirculation in the superficial capillary plexus. Conclusion: Early changes of the retinal function were documented in patients with recent MS and ON history with almost equal involvement of the retinal ganglion cells of the parvo-, mango- and koniocellular systems into the pathological process. For the first time, we established direct correlation between the parameters of microcirculation and morphometry of the inner retina. Clinical significance of the simultaneous detection in MS patients of the delay of P100 latency in the VEP and reduction of the thickness of the SCC and the retinal nerve fiber layer was shown. For citations: Lantukh E.P., Zueva M.V., Tsapenko I.V., et al. Microcirculatory and functional changes in the retina and visual channels in multiple sclerosis. Russian ophthalmological journal. 2017; 10 (3): 29-41. doi: 10.21516/2072-0076-2017-10-3-29-41 (in Russian).

&lt;p&gt;&lt;strong&gt;Optic neuritis is an inflammatory demyelinating disease of the optic nerve (ON) which is often associated with autoimmune diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder. Its relationship with MS is closely interwoven, as optic neuritis is commonly the first clinical sign of MS and is experienced by 60-70% of MS patients in the course of their disease. Disease occurs when white matter lesions appear on the ON, leading to axonal loss and atrophy of the retinal nerve fibre layer, potentially leading to permanent vision loss despite the individual recovering from the acute immune attack. There is no cure for MS-associated optic neuritis, and current immunomodulatory treatments for MS and optic neuritis focus only on preventing attacks and slowing disease progression, not repairing the damage that has already been done.&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;Treatments targeting the oligodendrocyte lineage - responsible for myelination of the central nervous system - are promising due to their potential to drive remyelination. Recent preclinical studies using models of demyelination have presented the kappa opioid receptor (KOPr) as a target for remyelination, with KOPr receptor agonists having been shown to promote oligodendrocyte precursor cell differentiation into oligodendrocytes and increase myelination. The current research investigated the ON features in the experimental autoimmune encephalomyelitis (EAE) model of demyelination and the effect of the clinically available KOPr agonist, nalfurafine, on myelination, immune infiltration, oligodendrocyte lineage cells, microglia, and astrocytes in the model. Techniques used were Black-Gold II and haematoxylin and eosin staining, and immunolabelling with anti-SOX10, -GST-pi, -IBA1, and -GFAP antibodies. It was shown that demyelination and immune infiltration occur, mature oligodendrocytes are fewer, while microglia and astrocyte numbers increase in ONs of EAE mice. Additionally, nalfurafine suppressed astrocyte GFAP expression in the EAE model.&lt;/p&gt;