Relation Of Vision To Global And Regional Brain MRI In Multiple Sclerosis
Wu GF, Schwartz ED, Lei T, Souza A, Mishra S, Jacobs DA, Markowitz CE, Galetta SL, Nano-Schiavi ML, Desiderio LM, Cutter GR, Calabresi PA, Udupa JK, Balcer LJ
Neurology 2007 Dec 4;69(23):2128-35
University of Pennsylvania School of Medicine, Departments of Neurology, Philadelphia, PA, USA
To examine the relation between low-contrast letter Acuity, an emerging Visual outcome for Multiple Sclerosis (MS) clinical trials, and Brain MRI abnormalities in an MS cohort.
T2 lesion volume and Brain Parenchymal Fraction were determined for whole Brain and within Visual pathway regions of interest. Magnetization Transfer Ratio Histograms were examined.
Vision testing was performed binocularly using low-contrast letter Acuity (2.5%, 1.25% contrast) and high-contrast Visual Acuity (VA).
Linear regression, accounting for age and disease duration, was used to assess the relation between Vision and MRI measures.
Patients (n = 45) were aged 44 +/- 11 years, with disease duration of 5 years (range < 1 to 21), Expanded Disability Status Scale score of 2.0 (0 to 6.0), and binocular Snellen Acuity of 20/16 (20/12.5 to 20/25).
The average T2 lesion volume was 18.5 mm(3). Patients with lower (worse) low-contrast letter Acuity and high-contrast VA scores had:
Greater T2 lesion volumes in Whole Brain (2.5% contrast: p = 0.004; 1.25%: p = 0.002; VA: p = 0.04)
Area 17 White Matter (2.5%: p < 0.001; 1.25%: p = 0.02; VA: p = 0.01)
Optic Radiations (2.5%: p = 0.001; 1.25%: p = 0.02; VA: p = 0.007).
Within Whole Brain, a 3-mm(3) increase in lesion volume corresponded, on average, to a 1-line worsening of low-contrast acuity, whereas 1-line worsening of high-contrast Acuity corresponded to a 5.5-mm(3) increase.
Low-contrast letter Acuity scores correlate well with Brain MRI lesion burden in Multiple Sclerosis (MS), supporting validity for this vision test as a candidate for clinical trials.
Disease in the PostGeniculate White Matter is a likely contributor to Visual Dysfunction in MS that may be independent of acute Optic Neuritis history.
Optic Nerve Magnetization Transfer Imaging And Measures Of Axonal Loss And Demyelination In Optic Neuritis
Trip SA, Schlottmann PG, Jones SJ, Li WY, Garway-Heath DF, Thompson AJ, Plant GT, Miller DH
Mult Scler 2007 Aug;13(7):875-9
Institute of Neurology, University College London, NMR Research Unit, Department of NeuroInflammation, London, UK
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.
The Relationship Between Hla-Drb1 Alleles And Optic Neuritis In Irish Patients And The Risk Of Developing Multiple Sclerosis
Tuwir I, Dunne C, Crowley J, Saddik T, Murphy R, Cassidy L
Br J Ophthalmol 2007 Oct;91(10):1288-92
The Royal Victoria Eye and Ear Hospital, Adelaide Road, Dublin 2, Ireland
To investigate the role of the Major Histocompatibility Complex in Irish patients with Optic Neuritis (ON) and determine whether HLA-DRB1 genotypes are a risk factor for the development of Multiple Sclerosis (MS) in such patients.
All patients were Caucasian, had Irish ancestry and had MRI of Brain and Optic Nerves within 2-3 weeks of presentation.
Patients were referred to a Neurologist if MRI findings were consistent with a diagnosis of MS.
HLA-DRB1 allele and phenotype frequencies for 78 patients with a clinical diagnosis of acute ON were compared with those for 250 healthy bone marrow donors.
An ON/MS positive patient was 3.4 times more likely than an ON/MS negative patient to be DRB1*15 positive.
No difference in age profile was detected between ON/MS positive and ON/MS negative patients or between the ON male and female subgroups.
No gender or HLA-DRB1 association was identified for ON/MS negative patients. Female gender was significantly increased among ON/MS positive patients with a p value of 0.0053.
DRB1*15 is a significant predisposing factor for ON. This ON patient cohort has also provided an opportunity to evaluate the relationship of HLA genotype with the risk of MS development.
The findings of this study indicate that Irish individuals presenting with ON and who are HLA DRB1*15 positive have a higher risk than HLA DRB1*15 negative patients of presenting with MRI findings indicative of MS.
This study has also demonstrated that female gender is a risk factor for developing MS in the Irish population.
Optic Neuritis Study Group
Brodsky M, Nazarian S, Orengo-Nania S, Hutton GJ, Buckley EG, Massey EW, Bhatti MT, Greer M, Goodwin J, Wall M, Savino PJ, Leist T, Miller NR, Irani D, Trobe JD, Cornblath W, Kaufman DI, Eggenberger E, Kupersmith MJ, Shults WT, McAllister L, Hamilton S, Beck RW, Dontchev M, Gal RL, Kollman C, Keltner JL, Smith CH
Arch Neurol 2008 Jun;65(6):727-32
To assess the risk of developing Multiple Sclerosis (MS) after Optic Neuritis and the factors predictive of high and low risk.
Subjects in the Optic Neuritis Treatment Trial, who were enrolled between July 1, 1988, and June 30, 1991, were followed up prospectively for 15 years, with the final examination in 2006.
Neurologic and Ophthalmologic examinations at 13 clinical sites.
Participants & Main Outcome Measures
Three hundred eighty-nine subjects with Acute Optic Neuritis. Development of MS and Neurologic Disability assessment.
The cumulative probability of developing MS by 15 years after onset of Optic Neuritis was 50% (95% confidence interval, 44%-56%).
And strongly related to presence of lesions on a baseline non-contrast-enhanced Magnetic Resonance Imaging (MRI) of the Brain.
Twenty-five percent of patients with no lesions on baseline Brain MRI developed MS during follow-up compared with 72% of patients with 1 or more lesions.
After 10 years, the risk of developing MS was very low for patients without baseline lesions but remained substantial for those with lesions.
Among patients without lesions on MRI, baseline factors associated with a substantially lower risk for MS included male sex, Optic Disc swelling, and certain atypical features of Optic Neuritis.
The presence of Brain MRI abnormalities at the time of an Optic Neuritis attack is a strong predictor of the 15-year risk of MS.
In the absence of MRI-detected lesions, male sex, Optic Disc swelling, and atypical clinical features of Optic Neuritis are associated with a low likelihood of developing MS.
This Natural History information is important when considering prophylactic treatment for MS at the time of a first acute onset of Optic Neuritis.