Mario L.R. Monteiro 1,
Danilo B. Fernandes 2,
Samira L. Apostolos-Pereira 3 and
Dagoberto Callegaro 3

Author Affiliations

1 Division of Ophthalmology and Laboratory of Investigation in Ophthalmology (LIM 33), University of Sao Paulo Medical School, Av. Angelica 1757 conj. 61, Sao Paulo, Sao Paulo, 01227-200, Brazil

2 Division of Ophthalmology and Laboratory of Investigation in Ophthalmology (LIM 33), University of Sao Paulo Medical School, Sao Paulo, Brazil

3 Department of Neurology, University of Sao Paulo Medical School, Sao Paulo, Brazil

Division of Ophthalmology and Laboratory of Investigation in Ophthalmology (LIM 33), University of Sao Paulo Medical School, Av. Angelica 1757 conj. 61, Sao Paulo, Sao Paulo, 01227-200, Brazil mlrmonteiro@terra.com.br

Abstract

Objective: To compare retinal nerve fiber layer (RNFL) and macular thickness measurements in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) with or without history of optic neuritis and in controls using Fourier-domain (FD) optical coherence tomography (OCT). Methods: Patients with MS (n=60), NMO (n=33), longitudinal extensive transverse myelitis (LETM) (n=28) and healthy controls (n=41) were submitted to ophthalmic examination, including automated perimetry, and to FD-OCT RNFL and macular thickness measurements. Five groups of eyes were compared: MS with or without previous optic neuritis, NMO, LETM and controls. Correlation between OCT and visual field (VF) findings was investigated. Results: With regard to most parameters, RNFL and macular thickness measurements were significantly smaller in eyes of each group of patients compared to controls. MS eyes with optic neuritis did not differ significantly from MS eyes without optic neuritis, but measurements were smaller in NMO eyes than in all other groups. RNFL (but not macular thickness) measurements were significantly smaller in LETM eyes than in controls. While OCT abnormalities were significantly correlated with VF loss in both NMO/LETM and MS, the correlation was much stronger in the former. Conclusion: Although FD-OCT RNFL and macular thickness measurements can reveal subclinical or optic neuritis-related abnormalities in both NMO-spectrum and MS patients, abnormalities are predominant in the macula of MS patients and in RFNL measurements in NMO patients. The correlation between OCT and VF abnormalities was stronger in NMO than in MS, suggesting the two conditions differ regarding structural and functional damage.

Copyright © 2012 by Association for Research in Vision and Ophthalmology

Continued at resource.

Thanks in advance for your help,

Bob Hunter

I think it would be very exciting!

Sent from my iPad

On May 6, 2012, at 8:45 AM, [email address removed] wrote:

> Neuromyelitis Optica: An Antibody-Mediated Disorder of the
> Central Nervous System
> Jiwon Oh andMichael Levy,
>
> Department of Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Pathology 509, Baltimore, MD 21287, USA
>
> Correspondence should be addressed to Michael Levy, [email address removed]
>
> Received 7 July 2011; Revised 4 October 2011; Accepted 13 October 2011
>
> Academic Editor: Philippe Cabre
>
> Copyright © 2012 J. Oh and M. Levy. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
>
> 1. Introduction
>
> Neuromyelitis optica (NMO) is a recurrent inflammatory disease that preferentially targets the optic nerves and spinal cord leading to blindness and paralysis.
>
> In 1870, Allbut was the first to report a case of NMO [1], but it was Devic who described the disorder in detail,and summarized 16 cases in the existing literature in 1894 [2]. Based on this initial description, historically, NMO has been regarded as a severe, generally monophasic disorderof the optic nerves and spinal cord and was thought tobe a variant of multiple sclerosis (MS). A convincing body of evidence in the past decade has established NMO as a
> distinct disease entity from MS. NMO is now recognized as a recurrent disease that largely targets the spinal cord and optic nerves but can also affect the brain as well. NMO occupies a unique position in the spectrum of inflammatory
> central nervous system demyelinating disorders in that it is the only such disorder that has an associated disease-specific antibody, aquaporin-4 antibody (AQP4 Ab), or NMOIgG. Recognition of this antibody has been instrumental in elucidating the underlying pathobiology and in guiding treatment options for NMO.
>
> 2. Clinical Features
>
> The hallmarks of NMO include bilateral optic neuritis and longitudinally extensive transverse myelitis. Woman and African Americans are over represented in the US patient population. NMO is associated with the NMO-IgG biomarker, which targets the aquaporin-4 water channel on astrocytes. The humoral pathology of NMO lesions include IgG and IgM deposits and infiltration by granulocytes suggesting that the NMO-IgG may be involved in the pathogenesis of disease. This review of the recent NMO literature covers the clinical features, epidemiology, radiology and pathology of disease and includes discussion of the important basic science research work in the field.
>
> Clinical features attributable to locations outside of the optic nerves and spinal cord can also occur in patients with NMO. Hypothalamic-pituitary axis dysfunction can manifest as hypersomnolence, hyponatremia, hypothermia, hypothyroidism, and hyperprolactinemia [8]. In addition, confusion, abrupt changes in level of consciousness, cortical blindness, and imaging findings suggestive of posterior reversible encephalopathy syndrome (PRES) have also been reported [9].
>
> The clinical course of NMO historically took one oftwo forms: monophasic or relapsing, with relapsing forms comprising approximately 80–90% of cases. However, after an index event, the distinction between monophasic and relapsing NMO is often difficult to make since relapses can occur many years after an event. In the vast majority of cases (∌80%), a relapse occurs by 2-3 years after the index event[3, 10]. Clinical features that may predict a relapsing course of disease include older age, female gender, less severe motor impairment with the initial myelitis event, and evidence of systemic autoimmunity [3].
>
> Clinical attacks typically progress over days, with varying degrees of recovery seen in the ensuing weeks to months. Recovery is usually incomplete, and most patients sustain residual disability, which increases with subsequent attacks [3]. Factors predictive of mortality in patients with relapsing NMO include the presence of other systemic autoimmune disorders, higher attack frequency in the first two years, and poor motor recovery following the index myelitis event [10, 11]. Longitudinal case series of NMO patents with followup ranging from 5 to 10 years have demonstrated that the majority of patients (47–100%) have significant ambulatory difficulties at follow-up. Residual visual deficits are also common, with >60% of patients reporting significant vision loss in at least one eye. Mortality due to respiratory failure has been reported to take place in up to 32% of patients [12, 13]. Of note, this mortality figure was derived from the original Mayo Clinic study [3], which took place prior to the widespread recognition of NMO and NMOSDs, and the patient population may have been biased with respect to clinical disease severity. Therefore, the prognosis of NMO may not be as grave as was reported in these earlier studies.
>
> In 1999, Wingerchuk et al. proposed diagnostic criteria for NMO which were based on clinical and radiographic features [3]. With the discovery of AQP4-Ab, these criteria were revised in 2006 to include the testing of this disease specific antibody. In addition, the necessary clinical features included were modified and simplified in an attempt to improve the diagnostic properties of the criteria. At present, the 2006 proposed diagnostic criteria for NMO consist of the presence of optic neuritis and transverse myelitis as well as 2 out of 3 of a contiguous spinal cord MRI lesion extending over more than 3 vertebral segments (i.e., longitudinally extensive), brain MRI notmeeting diagnostic criteria for MS, and NMO-IgG seropositive status [14]. These criteria are
> 99% sensitive and 90% specific for the diagnosis of NMO and have been independently validated in different patient populations [15].
>
> The recent literature suggests that in addition to its utility in the diagnosis of NMO, the presence of NMO-IgG may have a role in disease prognosis. In a prospective study of patients with longitudinally extensive transverse myelitis (LETM), 55% of those positive for NMO-IgG relapsed with recurrent LETM or optic neuritis, while none of the seronegative patients relapsed [4]. Similarly, in a series of patients with recurrent optic neuritis, the presence of NMOIgG
> heralded a 50% chance of developing transverse myelitis [16], while only 6.6% of seronegative patients developed transverse myelitis. More recently, Jarius et al. found that in acute monosymptomatic optic neuritis, 50% of NMO-IgG
> seropositive patients progressed to NMO within 12 months, while none of the seronegative patients progressed after a median follow-up of 26 months [17].
>
> In light of the fact that NMO is a disorder that has the potential to cause significant disability, the ability to recognize and differentiate NMO and related disorders from other demyelinating disorders is important from a clinical
> perspective. The term “NMO spectrum disorders” has been coined to reflect a variety of disorders thought to be related to NMO but do not quite meet the clinical diagnostic criteria for definite NMO. Disorders that are typically included in this classification are NMO-IgG seropositive limited forms of NMO (single or recurrent LETM, recurrent or simultaneous bilateral ON), Asian opticospinal MS (OSMS), optic neuritis or LETM associated with systemic autoimmune disease, and optic neuritis or myelitis associated with brain lesions typical of NMO (e.g., hypothalamic or brainstem lesions) [12]. Whether the NMO-IgG seronegative forms of these disorders are a forme fruste of classic NMO or whether they are variants of other autoimmune diseases is, at present, unclear. Until we are able to better identify with certainty that these are distinct disorders, the designation of NMO spectrum disorders is useful, as it has specific prognostic and therapeutic implications for these potentially related
> disorders.
>
> 3. Epidemiology
>
> NMO has a distinct epidemiological profile in comparison to MS. The median age of onset of NMO is typically in the fourth or fifth decade, which is older than the average age of onset ofMS. The age of onset can be quite variable, however, and NMO is occasionally seen in children and the elderly. There is a significant female predominance in both diseases, but it is even more polarized in NMO, with a female-to-male ratio ranging from 5–11 : 1 [3, 10, 13, 18].
>
> From a global perspective, NMO occurs much more commonly in nations with a predominately nonwhite population make-up, where it is a common cause of CNS demyelination. In Japan, up to 15–40% of MS is comprised of the opticospinal variant, which may be a synonymous disorder with NMO [19]. Lau et al. reported that up to 36% of MS cases in Hong Kong had selective involvement of the optic nerves and spinal cord [20], and NMO comprised
> 17% of possible MS cases in French Afro-Caribbeans in Martinique [21]. In a population-based study in Cuba, NMO comprised approximately 10% of demyelinating disorders [22]. In contrast, in countries consisting of a predominately white population, NMO comprised less than 2% of all demyelinating disorders, and the majority of cases occurred in white patients [23]. Similarly, in theMayo series, Wingerchuk et al. found that NMO still tends to occur predominately in white populations [3].
>
> Our experience at the NMO clinic at Johns Hopkins Medical Institution has shown a significant racial predilection for NMO with African American populations comprising approximately 50% of patients, which is clearly
> epidemiologically distinct from MS (unpublished data).
>
> Continued at resource:
>

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We hope to stay a part of the NMO community. though Collin's battle is over, we will still be here fighting for our NMO family. This fight is near & dear to our hearts. No one should go through what Collin went through & our new goal in life is to work to make this stop! We love you all!

We also greatly appreciate the Guthy-Jackson Foundation's willingness to honor our Super Hero by starting the "Collin McDaniel Hope Grant" for the purpose of Pediatric NMO research. It is an honor to our family to know our Collin will never be forgotten. Thank you so much to Victoria, Bill, Ali & all the others who have worked so hard.

Much Love,
Carey, Lisa, Angellyn & Mishelle McDaniel