Optic Neuritis In Multiple Sclerosis

  1. Effects of IntraVenous MethylPrednisolone on outcome in MRI-based prognostic subgroups in Acute Optic Neuritis
    Neurology 1998 Jan;50(1):230-237

  2. Optic Neuritis: Doppler ultrasonography compared with MR and correlated with Visual Evoked Potential assessments
    Acta Radiol 1998 May;39(3):243-8

  3. Functional MRI of the Visual Cortex and Visual testing in patients with previous Optic Neuritis
    Eur J Neurol 2002 May;9(3):277-86

  4. Irreversible disability and tissue loss in Multiple Sclerosis: a Conventional and Magnetization Transfer Magnetic Resonance imaging study of the Optic Nerves
    Arch Neurol 2002 Feb;59(2):250-5

  5. Continuing Optic Nerve Atrophy following Optic Neuritis: a serial MRI study
    Mult Scler 2002 Aug;8(4):339-42

  6. Functional Magnetic Resonance Imaging of the Cortical response to photic stimulation in humans following Optic Neuritis recovery
    NeuroSci Lett 2002 Sep 27;330(3):255-9

  7. Management of acute Optic Neuritis
    Lancet 2002 Dec 14;360(9349):1953-62

  8. Ophthalmology update for primary practitioners. Part I. Update on Optic Neuritis
    Dis Mon 2000 Aug;46(8):508-32

  9. The prognosis of idiopathic Optic Neuritis
    Neurol Sci 2000;21(4 Suppl 2):S865-9

  10. Dexamethasone and MethylPrednisolone in treatment of indirect traumatic Optic Neuropathy
    J Med Assoc Thai 2001 May;84(5):628-34

  11. Size-selective Neuronal changes in the Anterior Optic Pathways suggest a differential susceptibility to injury in Multiple Sclerosis
    Brain 2001 Sep;124(Pt 9):1813-20

  12. Optic Neuritis in an urban black African community
    Eye 2001 Aug;15(Pt 4):469-73


Effects Of IntraVenous MethylPrednisolone On Outcome In MRI-Based Prognostic Subgroups In Acute Optic Neuritis

Kapoor R, Miller DH, Jones SJ, Plant GT, Brusa A, Gass A, Hawkins CP, Page R, Wood NW, Compston DA, Moseley IF, McDonald WI
Neurology 1998 Jan;50(1):230-237
Institute of Neurology, Addenbrooke's Hospital, and Univ, Dept of Clinical Neurology, National Hospital for Neurology and NeuroSurgery, London, UK
PMID# 9443485; UI# 98103722

Treatment of Acute Optic Neuritis with Steroids has been shown to hasten Visual recovery without affecting the final degree of recovery.

However, MRI-clinical studies indicate that patients with long Optic Nerve lesions, particularly those that involve the Nerve within the Optic Canal, may have a worse prognosis for recovery of Vision.

Partly because such Lesions could lead to swelling and subsequent Ischemic Optic Nerve damage.

Steroids could have a selective beneficial effect on this subgroup of patients. The present randomized trial was designed to test this possibility.

Sixty-six patients with Acute Optic Neuritis received IV Saline or IV MethylPrednisolone. The Clinical, PsychoPhysical, ElectroPhysiologic, and MRI outcomes were assessed after 6 months.

Patients with short lesions presented earlier than those with long lesions (involving three or more 5-mm-thick slices of any part of the Optic Nerve, as well as its IntraCanalicular portion), and lesion length was significantly less in patients presenting within a week of onset of symptoms.

Lesions also tended to lengthen during follow-up in individual patients. Treatment did not limit lesion length in either the long or short lesion subgroup and had no significant effect on final Visual outcome.

We conclude that Steroids do not improve Visual outcome or lesion length in patients with Acute Optic Neuritis.


Optic Neuritis: Doppler Ultrasonography Compared With MR And Correlated With Visual Evoked Potential Assessments

Elvin A, Andersson T, Soderstrom M
Acta Radiol 1998 May;39(3):243-8
Karolinska Hospital, Dept of Diagnostic Radiology, Stockholm, Sweden
PMID# 9571937; UI# 98233430

To establish the role of Doppler UltraSonography (US) in the examination of patients with acute unilateral Optic Neuritis.

Material And Methods
Twenty-five patients with a clinical diagnosis of Optic Neuritis were prospectively evaluated and 18 of them were included in the study.

The inclusion criteria were MR findings of unilateral disease and age below 50 years.

All patients were examined with MR in order to objectively detect, localize and measure the Optic Nerve lesions and in order to exclude patients with unidentifiable Optic Nerve involvement.

Evaluation with US was performed to determine Nerve Morphology, Nerve swelling, and resistance to flow in the Central Retinal Artery. The patients' contralateral Optic Nerve served as an internal control.

The US findings were correlated to the degree of Visual impairment, both initially and at follow-up. Visual Evoked Potential (VEP) assessments were also performed in 16 patients.

A statistically significant difference was found in the Optic Nerve diameter and in the resistance to flow in the Central Retinal Artery between the affected and unaffected eyes.

Patients with a prolonged impairment of Visual Acuity initially had a more swollen nerve and an increased resistance to flow in the affected Optic Nerve.

Prognostic information was also gathered solely by evaluating the unaffected nerve diameter: patients who normally had thinner Optic Nerves had a more severe form of Optic Neuritis.

VEP assessments were positive in all patients investigated.

Doppler US can be used together with a VEP assessment as an indicator of the disease process in Acute Optic Neuritis. These methods offer a potential for monitoring patients over time.


Functional MRI Of The Visual Cortex And Visual Testing In Patients With Previous Optic Neuritis

Langkilde AR, Frederiksen JL, Rostrup E, Larsson HB
Eur J Neurol 2002 May;9(3):277-86
Danish Research Centre for Magnetic Resonance, Hvidovre University Hospital, Copenhagen, Norway
PMID# 11985636

The volume of Cortical activation as detected by Functional Magnetic Resonance Imaging (fMRI) in the Visual Cortex has previously been shown to be reduced following Optic Neuritis (ON).

In order to understand the cause of this change, we studied the Cortical activation, both the size of the activated area and the signal change following ON, and compared the results with results of NeuroOphthalmological testing.

We studied nine patients with previous acute ON and 10 healthy persons served as controls using fMRI with visual stimulation.

In addition to a reduced activated volume, patients showed a reduced Blood Oxygenation Level Dependent (BOLD) signal increase and a greater asymmetry in the Visual Cortex, compared with controls.

The volume of Visual Cortical activation was significantly correlated to the result of the contrast sensitivity test.

The BOLD signal increase correlated significantly to both the results of the contrast sensitivity test and to the Snellen Visual Acuity.

Our results indicate that fMRI is a useful method for the study of ON, even in cases where the Visual Acuity is severely impaired.

The reduction in activated volume could be explained as a reduced Neuronal input; however, the greater asymmetry might point to a Cortical reorganization as a consequence of Neuronal damage.

Future fMRI studies in ON will add to the understanding of the Neural adaptive behavior following ON.


Irreversible Disability And Tissue Loss In Multiple Sclerosis: A Conventional And Magnetization Transfer Magnetic Resonance Imaging Study Of The Optic Nerves

Inglese M, Ghezzi A, Bianchi S, Gerevini S, Sormani MP, Martinelli V, Comi G, Filippi M
Arch Neurol 2002 Feb;59(2):250-5
Scientific Institute and University Ospedale San Raffaele, Department of NeuroScience, NeuroImaging Research Unit, Via Olgettina 60, 20132 Milan, Italy
PMID# 11843696

To assess, by Magnetic Resonance Imaging, the volumes and Magnetization Transfer Ratio (MTR) values of Optic Nerves (ONs) from patients with Multiple Sclerosis (MS) who had incomplete or no Visual recovery after Optic Neuritis (ON).

And, to compare these quantities with those derived from ONs from patients with MS who showed a marked clinical recovery after Optic Neuritis, ONs from healthy volunteers, and ONs from patients with Leber's Hereditary Optic Neuropathy (LHON).

Conventional and Magnetization Transfer Magnetic Resonance images of the ONs were obtained from 30 patients with MS, 18 healthy volunteers, and 10 patients with LHON.

The ON from patients with MS were classified as clinically unaffected (n = 18); clinically affected with recovery (n = 20; Visual Acuity > or =20/25 at least 6 months after Optic Neuritis).

And clinically affected with incomplete or no recovery (n = 22; Visual Acuity < 20/25 at least 6 months after Optic Neuritis). The ON volumes and MTR values were measured.

Volumes (P =.002) and MTR values (P< .001) of the ONs from patients with MS and incomplete or no recovery were both lower than those of the ONs from patients with MS and recovery, but not different from those of the ONs from patients with LHON.

Volumes and MTR values of the affected ONs from patients with MS and recovery did not differ from those of clinically unaffected ONs, which were similar to those of healthy volunteers.

These findings suggest that, in patients with MS, NeuroDegeneration is associated with persistent functional deficits secondary to incomplete recovery from relapses.


Continuing Optic Nerve Atrophy Following Optic Neuritis: A Serial MRI Study

Hickman SJ, Brierley CM, Brex PA, MacManus DG, Scolding NJ, Compston DA, Miller DH
Mult Scler 2002 Aug;8(4):339-42
Institute of Neurology, NMR Research Unit, University College London, UK
PMID# 12166505

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.


Functional Magnetic Resonance Imaging Of The Cortical Response To Photic Stimulation In Humans Following Optic Neuritis Recovery

Toosy AT, Werring DJ, Bullmore ET, Plant GT, Barker GJ, Miller DH, Thompson AJ
NeuroSci Lett 2002 Sep 27;330(3):255-9
Institute of Neurology, NMR Research Unit, Queen Square, London WC1N 3BG, UK
PMID# 12270641

Recovery from Optic Neuritis has been shown to be associated with an abnormal functional MRI (fMRI) response following exposure of the Eye to an Epoch based (ON-OFF design) flickering Photic stimulus.

Visual Cortex activation is reduced during Photic stimulation, while ExtraOccipital areas are extensively activated with a peak blood oxygen level dependent response during the OFF phase of the stimulus paradigm.

We performed a further fMRI experiment to determine whether the abnormal ExtraOccipital response is a phase-specific phenomenon or whether it results from a delayed HaemoDynamic response.

A cohort of patients that recovered from Optic Neuritis was studied, this time using a longer Photic stimulation Epoch (40 s).

The ExtraOccipital response again peaked during the baseline condition, indicating that the phenomenon is phase dependent.

Our results also reinforce the important findings of ExtraOccipital activation following Optic Neuritis which may represent an adaptive reorganization of the Cerebral response.

Copyright 2002 Elsevier Science Ltd.


Management Of Acute Optic Neuritis

Hickman SJ, Dalton CM, Miller DH, Plant GT
Lancet 2002 Dec 14;360(9349):1953-62
Institute of Neurology, NMR Research Unit, University College London, London, UK
PMID# 12493277

Optic Neuritis is a common condition that causes reversible loss of Vision. It can be clinically isolated or can arise as one of the manifestations of Multiple Sclerosis.

Occasional cases are due to other causes, and in these instances management can differ radically.

The treatment of Optic Neuritis has been investigated in several trials, the results of which have shown that CorticoSteroids speed up the recovery of Vision without affecting the final Visual outcome.

Other aspects of management, however, are controversial, and there is uncertainty about when to investigate and when to treat the condition.

Here we review the diagnostic features of Optic Neuritis, its differential diagnosis, and give practical guidance about management of patients.

The condition's association with Multiple Sclerosis will be considered in the light of studies that define the risk for development of Multiple Sclerosis and with respect to results of trials of disease-modifying drugs in these individuals.


Ophthalmology Update For Primary Practitioners. Part I. Update On Optic Neuritis

Granadier RJ
Dis Mon 2000 Aug;46(8):508-32
Beaumont Eye Institute, William Beaumont Hospital, Royal Oak, Michigan, USA
PMID# 10969715

Optic Neuritis is a common cause of acute Visual Loss. It is typified by sudden onset of Visual Impairment and Pain with eye movements, followed by spontaneous recovery of Vision over several months.

Pathologically, Optic Neuritis is an acute DeMyelinating event affecting the Optic Nerve. Objective physical findings are typically few, including an Afferent Pupillary Defect (Marcus-Gunn Pupil).

Whereas, subjective PsychoPhysical findings abound (ie, Diminished Central Visual Acuity, Color Vision, Decreased Contrast Sensitivity, and Visual Field Abnormalities [Central Scotoma]).

These characteristics have made the diagnosis of Optic Neuritis based solely on clinical grounds disquieting to practitioner and patient alike.

In addition, the fact that Optic Neuritis is often associated with Multiple Sclerosis as the first clinical manifestation of disease, gives further reason for both patient and physician anxiety.

The serious nature of Visual Loss and the consequences of making the diagnosis of Optic Neuritis has given rise to extensive testing and expensive treatments.

    This review is intended to explore our current state of knowledge with regard to:
    1. Clinical presentation
    2. Ancillary testing
    3. Therapeutic intervention
    4. Associated disease
      • specifically the risk for Multiple Sclerosis in the patient who presents with an acute Optic Neuritis

Finally, a suggestion guide for informing the patient and addressing his or her concerns will be presented.


The Prognosis Of Idiopathic Optic Neuritis

Ghezzi A, Martinelli V, Rodegher M, Zaffaroni M, Comi G
Neurol Sci 2000;21(4 Suppl 2):S865-9
Multiple Sclerosis Center, Gallarate Hospital, University of Milan, VA, Italy
PMID# 11205365

We evaluated the risk of developing Clinically Definite Multiple Sclerosis (CDMS) after acute isolated Optic Neuritis in 102 patients in a follow-up study (duration 6.5 +/- 2.0 years).

The probability of CDMS was 13% after 2 years, 30% after 4 years, 38% after 6 years, and 49% after 8 and 10 years.

CDMS occurred in 42 (59%) of 71 patients with Brain lesions detected with Magnetic Resonance Imaging (MRI). No patient with normal MRI exam developed the disease.

Patients with 3 or more MRI-detected lesions presented a shorter first interattack interval and a higher relapse rate compared to subjects with only 1 or 2 lesions. The predictive value of CSF examination and of Evoked Potentials was poor.


Dexamethasone And MethylPrednisolone In Treatment Of Indirect Traumatic Optic Neuropathy

Kitthaweesin K, Yospaiboon Y
J Med Assoc Thai 2001 May;84(5):628-34
Khon Kaen University, Faculty of Medicine, Department of Ophthalmology, Thailand
PMID# 11560210

A randomized, double blind study was carried out to compare the efficacy of Dexamethasone and MethylPrednisolone in the treatment of indirect traumatic Optic Neuropathy.

Twenty-one patients, 20 male and 1 female, were diagnosed as having suffered from indirect traumatic Optic Neuropathy. The time from injury to treatment was within 7 days.

The average age was 26.38 +/- 11.89 years. The most common cause of injury was Motor Vehicle Accident (MVA). Associated head and MaxilloFacial injury were reported 43.48 and 34.78 per cent, respectively.

Before treatment, no light perception was detected in 19.05 per cent of the participants. Treatments were randomized: ten patients received Dexamethasone intravenously for 72 hours and 11 MethylPrednisolone.

The Best Corrected Visual Acuities (BCVA) were determined using the Snellen Chart before and 1, 2, 3, 7, 14 and 60 days after treatment.

Three or more lines of improvement of the BCVA, were found in 70 and 67 per cent of patients treated with Dexamethasone, and 45.45 and 33.33 per cent of patients treated with MethylPrednisolone, at 2 weeks and 2 months, respectively.

There were no significant differences in age, cause of injury, injury to treatment interval, initial BCVA and Visual improvement between the two groups.


Size-Selective Neuronal Changes In The Anterior Optic Pathways Suggest A Differential Susceptibility To Injury In Multiple Sclerosis

Evangelou N, Konz D, Esiri MM, Smith S, Palace J, Matthews PM
Brain 2001 Sep;124(Pt 9):1813-20
University of Oxford, Centre for Functional Magnetic Resonance Imaging of the Brain, UK
PMID# 11522583

Axonal damage is found in both acute and chronic lesions of Multiple Sclerosis. Direct Axon counting in post-mortem tissue has suggested that smaller Axons might have a greater susceptibility to damage, but methodological limitations have precluded unequivocal interpretation.

However, as Neuronal and Axonal sizes are linked and Neuronal changes would be expected with Retrograde or TransSynaptic Degeneration following Axon injury.

We hypothesized that an alternative strategy for studying this phenomenon would be to define Multiple Sclerosis-associated changes in Neurons.

To test this hypothesis, we measured both Axonal Loss and Neuronal size changes in the Anterior Optic Pathway [including the Optic Nerve (ON), Optic Tract (OT) and Lateral Geniculate Nucleus] of the Brains of eight patients who died with Multiple Sclerosis and in eight control Brains.

The ONs and OTs in Brains from the Multiple Sclerosis patients showed a trend to smaller mean cross-sectional areas (ON, Multiple Sclerosis = 6.84 mm(2), controls = 9.25 mm(2); and OT, Multiple Sclerosis = 6.45 mm(2), controls = 7.94 mm(2), P = 0.08).

And, had reduced Axonal densities (ON, Multiple Sclerosis = 1.1 x 10(5)/mm(2), controls = 1.7 x 10(5)/mm(2); and OT, Multiple Sclerosis = 1.4 x 10(5)/mm(2), controls = 1.8 x 10(5)/mm(2), P = 0.006).

Estimated total Axonal counts were reduced by 32 (OT)-45% (ON) in the patients relative to controls (ON, Multiple Sclerosis = 8.1 x 10(5) Axons, controls = 14.8 x10(5), P = 0.05; and OT, Multiple Sclerosis = 9.1 x 10(5), controls = 13.3 x 10(5), P = 0.02).

The size distributions of the MagnoCellular Cells in the Lateral Geniculate Nucleus were similar for the two groups, but in Multiple Sclerosis Brains the ParvoCellular Cells were significantly smaller.

(Mean sizes: Multiple Sclerosis = 226 microm (2), controls = 230 microm(2), P < 0.001) and had a larger variation in size, suggesting a greater proportion of Atrophic Neurons.

Axon Loss in the Optic Nerves of Multiple Sclerosis patients correlated strongly with measures of increased dispersion of cell sizes in the ParvoCellular layer (r = 0.8, P < 0.04).

These data demonstrate that both Atrophy and decreased density contribute to the substantial Axonal Loss in the Anterior Visual Pathway of these patients.

This appears related to a relatively selective Atrophy of the smaller Neurons of the ParvoCellular layer in the Lateral Geniculate Nucleus, supporting the hypothesis that smaller Axons may be preferentially susceptible to injury in Multiple Sclerosis.


Optic Neuritis In An Urban Black African Community

Pokroy R, Modi G, Saffer D
Eye 2001 Aug;15(Pt 4):469-73
University of Witwatersrand, Department of Neurology, Baragwanath Chris Hani Hospital, Johannesburg-Soweto, South Africa
PMID# 11767021

To describe the clinical profile of Idiopathic Optic Neuritis in South African blacks.

South African black patients with acute isolated idiopathic Optic Neuritis, treated and followed for at least 3 months at a large medical center, were studied.

Exclusion criteria were other causes of Optic Neuropathy (such as Ischaemic Optic Neuropathy, Toxins or Leber's Hereditary Optic Neuropathy); all causes of Optic Neuritis (such as HIV, NeuroSyphilis, Sarcoid or Connective Tissue Disease); Neurological Disease outside of the Optic Nerves; and any race other than South African black.

Patients underwent extensive Ophthalmic, Neurological, Radiological, CerebroSpinal Fluid and blood assessment.

Eighteen eyes of 10 patients were studied. The mean age was 35.7 years and 9 patients were female. Only 2 patients had truly UniLateral Optic Neuritis, the other 8 having either BiLaterally simultaneous or consecutive disease.

Presenting Visual Acuity (VA) was less than 6/60 in 17 of 18 Eyes, with severe DysChroMatopsia in all Eyes. Fifteen Eyes had Optic Disc swelling. All patients were treated with CorticoSteroids.

After at least 3 months follow-up only 6 Eyes recovered VA of 6/12 or better, with only 3 Eyes recovering Color Vision of 10/13 or better on Ishihara plate testing. No patient had Multiple Sclerosis (MS) on presentation, nor developed MS on follow-up.

Idiopathic Optic Neuritis in black South Africans differs from that in whites.

The higher prevalence of BiLateral cases and of Optic Disc swelling, the weaker association with MS and the extremely poor Visual outcome distinguish Optic Neuritis in black South Africans.

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