ABSTRACT
Acute disseminated encephalomyelitis (ADEM) is one characteristic manifestation of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). A previously healthy man presented with retro-orbital headache and urinary retention 14 days after Tdap vaccination. Brain and spine MRI suggested a CNS demyelinating process. Despite treatment with IV steroids, he deteriorated, manifesting hemiparesis and later impaired consciousness, requiring intubation. A repeat brain MRI demonstrated new bilateral supratentorial lesions associated with venous sinus thrombosis, hemorrhage, and midline shift. Anti-MOG antibody was present at a high titer. CSF IL-6 protein was >2,000 times above the upper limits of normal. He improved after plasma exchange, then began monthly treatment alone with anti-IL-6 receptor antibody, tocilizumab, and has remained stable. This case highlights how adult-onset MOGAD, like childhood ADEM, can rapidly become life-threatening. The markedly elevated CSF IL-6 observed here supports consideration for evaluating CSF cytokines more broadly in patients with acute MOGAD.
Subject(s)
Encephalomyelitis, Acute Disseminated , Male , Adult , Humans , Child , Interleukin-6/metabolism , Myelin-Oligodendrocyte Glycoprotein , Brain/pathology , Cytokines/metabolismABSTRACT
Introduction: Multiple sclerosis (MS) causes focal lesions of immune-mediated demyelinating events followed by slow progressive accumulation of disability. Over the past 2 decades, multiple medications have been studied and approved for use in MS. Most of these agents work by modulating or suppressing the peripheral immune system. Siponimod is a newer-generation sphingosine 1 phosphate (S1P) receptor modulator that internalizes S1P1 receptors, thereby inhibiting efflux of lymphocytes from lymph nodes and thymus. There are promising data suggesting that it may also have a direct neuroprotective property independent of peripheral lymphocytopenia.Areas covered: We reviewed the pharmacology and the clinical and radiological effects of siponimod.Expert opinion: The selective effect of siponimod on the S1P1 and S1P5 receptors offers a favorable side-effect profile and transient bradycardia can be avoided by dose titration. A phase-II study showed that siponomod has dose-dependent beneficial effects in patients with relapsing remitting disease. The results of a phase-III study suggest that siponimod may be beneficial in secondary progressive MS, at least in patients with disease activity.
Subject(s)
Azetidines/administration & dosage , Benzyl Compounds/administration & dosage , Multiple Sclerosis/drug therapy , Sphingosine 1 Phosphate Receptor Modulators/administration & dosage , Animals , Azetidines/adverse effects , Azetidines/pharmacology , Benzyl Compounds/adverse effects , Benzyl Compounds/pharmacology , Dose-Response Relationship, Drug , Humans , Multiple Sclerosis/physiopathology , Sphingosine 1 Phosphate Receptor Modulators/adverse effects , Sphingosine 1 Phosphate Receptor Modulators/pharmacology , Sphingosine-1-Phosphate Receptors/drug effects , Sphingosine-1-Phosphate Receptors/metabolismABSTRACT
Established cell lines are a critical research tool that can reduce the use of laboratory animals in research. Certain strains of genetically modified mice, such as Atm(-/-) and p53(-/-) consistently develop thymic lymphoma early in life (1,2), and thus, can serve as a reliable source for derivation of murine T-cell lines. Here we present a detailed protocol for the development of established murine thymic lymphoma T-cell lines without the need to add interleukins as described in previous protocols (1,3). Tumors were harvested from mice aged three to six months, at the earliest indication of visible tumors based on the observation of hunched posture, labored breathing, poor grooming and wasting in a susceptible strain (1,4). We have successfully established several T-cell lines using this protocol and inbred strains ofAtm(-/-) [FVB/N-Atm(tm1Led)/J] (2) and p53(-/-) [129/S6-Trp53(tm1Tyj)/J] (5) mice. We further demonstrate that more than 90% of the established T-cell population expresses CD3, CD4 and CD8. Consistent with stably established cell lines, the T-cells generated by using the present protocol have been passaged for over a year.
