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ABSTRACT: A 42-year-old African American woman with a 5-year history of neuromyelitis optica was found to have an incongruous homonymous hemianopia. Optical coherence tomography (OCT) showed corresponding left homonymous hemimacular thinning. Magnetic resonance imaging of the brain demonstrated a demyelinating lesion in the left optic tract (OT) just anterior to the lateral geniculate nucleus and diffusion tensor magnetic resonance tractography confirmed axonal fiber loss in the left OT. This case illustrates the complementary and confirmatory roles of visual field testing, macular OCT, and neuroimaging in an OT lesion, which caused selective hemimacular thinning through retrograde degeneration.
Journal of neuro-ophthalmology: the official journal of the North American Neuro-Ophthalmology Society 05/2012; 32(2):150-3. · 1.09 Impact Factor
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ABSTRACT: Neuromyelitis optica (NMO) is characterized by selective inflammation of the spinal cord and optic nerves but is distinct from multiple sclerosis (MS). Interferon (IFN)-β mitigates disease activity in MS, but is controversial in NMO, with a few reports of disease worsening after IFN-β therapy in this highly active disease. In systemic lupus erythematosus (SLE), IFNs adversely affect disease activity. This study examines for the first time whether serum IFN-α/β activity and IFN-β-induced responses in peripheral blood mononuclear cells (MNC) are abnormally elevated in NMO, as they are in SLE, but contrast to low levels in MS.
Serum type I IFN-α/β activity was measured by a previously validated bioassay of 3 IFN-stimulated genes (RT-PCR sensitivity, 0.1 U/ml) rather than ELISA, which has lower sensitivity and specificity for measuring serum IFNs. IFN responses in PBMNC were assessed by in vitro IFN-β-induced activation of phospho-tyrosine-STAT1 and phospho-serine-STAT1 transcription factors, and MxA proteins using Western blots.
Serum IFN-α/β activity was highest in SLE patients, followed by healthy subjects and NMO, but was surprisingly low in therapy-naïve MS. In functional assays in vitro, IFN-β-induced high levels of P-S-STAT1 in NMO and SLE, but not in MS and controls. IFN-β-induced MxA protein levels were elevated in NMO and SLE compared to MS.
Serum IFN activity and IFN-β-induced responses in PBMNC are elevated in SLE and NMO patients versus MS. This argues for similarities in pathophysiology between NMO and SLE and provides an explanation for IFN-induced disease worsening in NMO.
Journal of the neurological sciences 02/2012; 313(1-2):48-53. · 2.32 Impact Factor
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ABSTRACT: Neuromyelitis optica is a central nervous system disease characterized by optic neuritis and transverse myelitis. It is a devastating illness, and early treatment may prevent future relapses and severe disability. However, there is much variability in protocols used for treatment. In limited studies, rituximab has shown efficacy in adult neuromyelitis optica patients. There is a paucity of literature on the efficacy and tolerability of rituximab in the pediatric population. The authors report the use of rituximab in 2 pediatric patients with neuromyelitis optica, demonstrating its efficacy, dosing, and tolerability. This report may be a useful guide for administering rituximab safely in pediatric neuromyelitis optica patients.
Journal of child neurology 02/2011; 26(2):244-7. · 1.59 Impact Factor
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ABSTRACT: This update includes topics relating to the treatment of multiple sclerosis (MS) for the ophthalmologist.
Despite investigation into numerous genetic and environmental factors, the cause of MS remains elusive. MS is a disease of the central nervous system that mainly affects young people and usually progresses over time, leading to disability in multiple areas, including mobility, cognition, affect and vision. It is likely that, as novel MS treatments are introduced, there will be a greater interest in tracking visual function and monitoring for visual complications.
Current therapies in MS include interferon, glatiramer, natalizumab and mitoxantrone. Other MS treatments are imminent, and include oral medications, monoclonal antibodies and chemotherapy. Treatment of the visual symptoms in MS and the side effects of MS therapies are reviewed in this article.
Current opinion in ophthalmology 11/2009; 20(6):476-81. · 2.49 Impact Factor
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ABSTRACT: Several lines of evidence link immunosuppression to inflammation in patients with multiple sclerosis (MS) and provide a rationale for the increasing use of immunosuppressive drugs in the treatment of MS. Treatment-refractory, clinically active MS can quickly lead to devastating and irreversible neurological disability and treating these patients can be a formidable challenge to the clinician. Patients with refractory MS have been treated with intense immunosuppression, such as cyclophosphamide or mitoxantrone, or with autologous haematopoeitic stem cell transplants. Evidence shows that intense immunosuppression might be effective in patients who are unresponsive to immunomodulating therapy, such as interferon beta and glatiramer acetate. Natalizumab, a new addition to the armamentarium for treating MS, might also have a role in the treatment of this MS phenotype. This Review describes the use of intense immunosuppressant drugs and natalizumab in patients with rapidly worsening MS and provides clinicians with guidelines for the use of these drugs in this patient group.
The Lancet Neurology 03/2008; 7(2):173-83. · 23.46 Impact Factor
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ABSTRACT: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). In the last 12 years, there has been a proliferation of studies elucidating the immune mechanisms that mediate tissue damage in MS. Interferons (IFNs) have an important role in regulating innate and adaptive immune responses. They decrease pro-inflammatory responses such as the autoimmunity in MS, but other autoimmune responses such as systemic lupus erythematosus (SLE) may be exacerbated. This review offers a general overview of the biological properties of IFNs, effects on immune cells, and clinical effectiveness in MS treatment. IFN signaling is complex, from receptor binding events to the generation of effector mechanisms that dampen inflammation. Immune cell function is altered in MS. IFN treatment of MS patients ameliorates immune dysfunction, but not completely. The incomplete resolution of immune dysfunction by IFNs partly explains their significant, but modest therapeutic effects. This observation also suggests that there are immune mechanisms in MS that are resistant to IFN therapy. In MS, abnormalities may exist at several points along the IFN signaling pathway, including molecular defects in the IFN second messenger system. Currently, several studies are ongoing evaluating ways of potentiating IFN effects. IFNs were the first agents to show clinical efficacy in treatment of MS. More than a decade of experience with IFNs has showed continued clinical efficacy over time. In the near future, IFNs will continue to play a major role in MS.
Pharmacology [?] Therapeutics 05/2006; 110(1):35-56. · 8.56 Impact Factor
