Purpose of review
The purpose of this review is to summarize current understanding regarding the treatment of myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated demyelination in ...children. Emphasis is placed on the unique obstacles we face when predicting the risk of relapse and the important implications of such challenges when planning treatment protocols.
Recent findings
MOG-Abs are consistently identified in a range of acquired demyelinating syndromes (ADS) in adults and children with a clinical phenotype distinct of MS and AQP4-Ab neuromyelitis optica spectrum disorder. Although initially thought to be associated with a benign disease, recent reports of children who are treatment-resistant and developed progressive disability over time raise important questions about how children with relapsing MOG-Ab disease should be managed.
Summary
MOG-Abs are common in children with ADS with both monophasic and relapsing disease courses. Treatment of patients with MOG-Ab-associated demyelination includes management of acute relapses and chronic immunotherapy for those with relapsing disease. Emerging consensus supports distinction of treatment strategies from those typically used for relapsing remitting MS, and several groups debate whether to follow treatment protocols akin to those for AQP4-Ab NMOSD. A key challenge remains predicting the severity of the disease at onset. Collaborative international consensus to derive shared clinical evaluative platforms standardized biological and neuroimaging protocols which can be used clinically, and partnered research programs are required to advance personalized treatment for children with MOG-Ab-associated demyelination.
Paediatric multiple sclerosis (MS) is associated with higher relapse rate, rapid magnetic resonance imaging lesion accrual early in the disease course and worse cognitive outcome and physical ...disability in the long term compared to adult-onset disease. Current treatment strategies are largely centre-specific and reliant on adult protocols. The aim of this review is to examine which treatment options should be considered first line for paediatric MS and we attempt to answer the question if injectable first-line disease-modifying therapies (DMTs) are still an optimal option. To answer this question, we review the effects of early onset disease on clinical course and outcomes, with specific considerations on risks and benefits of treatments for paediatric MS. Considering the impact of disease activity on brain atrophy, cognitive impairment and development of secondary progressive MS at a younger age, we would recommend treating paediatric MS as a highly active disease, favouring the early use of highly effective DMTs rather than injectable DMTs.
During the Holocaust, poets went to extraordinary lengths to write their poems and transmit them. Poems that were written during those years were often buried in the ground, stitched into clothing, ...smuggled out of prisons, or graffitied onto walls. These object documents carried more than facts about these events; they carried the feeling of living through these events. This research explores the last poems of four Holocaust poets, Władysław Szlengel, Selma Meerbaum-Eisinger, Hannah Szenes, and Abramek Koplowicz, investigating not only the poems but their object-ness and their stories of transference. These poems, like urgent postcards, deliver messages to a family, to a community, to the world. They ask―what does it mean to write a poem as a last will and testament?
Rules of Engagement HACOHEN, YAEL S.
Ploughshares,
12/2022, Letnik:
48, Številka:
4
Journal Article, Magazine Article
Hacohen examines the war poetry of Denise Levertov who claimed that, like a poem, peace cannot be there ahead of itself. Levertov, a lyrical poet of great repute known primarily for her poems on ...family life, nature, and religious themes, deserves recognition for her substantial contribution to the canon of war poetry, a canon of literature almost entirely written by men. Levertov grew up in an intensely politically and socially aware environment. She was born between the two world wars, on October 24, 1923, in the town of Ilford, Essex, in England. She was the daughter of Beatrice Adelaide Spooner-Jones, a schoolteacher of Welsh heritage with artistic proclivities, and the Reverend Paul Philip Levertoff, a converted Russian Hassidic Jew, who served as a priest in the Church of England.
N-methyl-D-aspartate receptor antibody (NMDAR-Ab) encephalitis is a well-recognised clinico-immunological syndrome that presents with neuropsychiatric symptoms cognitive decline, movement disorder ...and seizures. This study reports the clinical features, management and neurological outcomes of paediatric NMDAR-Ab-mediated neurological disease in the UK.
A prospective surveillance study. Children with NMDAR-Ab-mediated neurological diseases were voluntarily reported to the British Neurological Surveillance Unit (BPNSU) from November 2010 to December 2011. Initial and follow-up questionnaires were sent out to physicians.
Thirty-one children fulfilled the criteria for the study. Eight presented during the study period giving an incidence of 0.85 per million children per year (95% CI 0.64 to 1.06); 23 cases were historical. Behavioural change and neuropsychiatric features were present in 90% of patients, and seizures and movement disorders both in 67%. Typical NMDAR-Ab encephalitis was reported in 24 children and partial phenotype without encephalopathy in seven, including predominantly psychiatric (four) and movement disorder (three). All patients received steroids, 22 (71%) received intravenous immunoglobulin, 9 (29%) received plasma exchange,and 10 (32%) received second-line immunotherapy. Of the 23 patients who were diagnosed early, 18 (78%) made a full recovery compared with only 1 of 8 (13%) of the late diagnosed patients (p=0.002, Fisher's exact test). Seven patients relapsed, with four needing additional second-line immunotherapy.
Paediatric NMDAR-Ab-mediated neurological disease appears to be similar to adult NMDAR-Ab encephalitis, but some presented with a partial phenotype. Early treatment was associated with a quick and often full recovery.
To assess the clinical and immunologic findings in children with voltage-gated potassium channel (VGKC)-complex antibodies (Abs).
Thirty-nine of 363 sera, referred from 2 pediatric centers from 2007 ...to 2013, had been reported positive (.100 pM) for VGKC-complex Abs. Medical records were reviewed retrospectively and the patients’ condition was independently classified as inflammatory (n 5 159) or noninflammatory (n 5 204). Positive sera (.100 pM) were tested/retested for the VGKC complex Ab–positive complex proteins LGI1 and CASPR2, screened for binding to live hippocampal neurons, and 12 high-titer sera (.400 pM) tested by radioimmunoassay for binding to VGKC Kv1 subunits with or without intracellular postsynaptic density proteins.
VGKC-complex Abs were found in 39 children, including 20% of encephalopathies and 7.6% of other conditions (p 5 0.001). Thirty children had inflammatory conditions and 9 had noninflammatory etiologies but titers.400 pM (n512) were found only in inflammatory diseases (p , 0.0001). Four sera, including from 2 children with coexisting NMDA receptor Abs and one with Guillain-Barré syndrome and Abs to both LGI1 and CASPR2, bound to hippocampal neurons. None of the sera bound detectably to VGKC Kv1 subunits on live HEK cells, but 4 of 12 .400 pM sera immunoprecipitated VGKC Kv1 subunits, with or without postsynaptic densities, extracted from transfected cells.
Positive VGKC-complex Abs cannot be taken to indicate a specific clinical syndrome in children, but appear to be a nonspecific biomarker of inflammatory neurologic diseases, particularly of encephalopathy. Some of the Abs may bind to intracellular epitopes on the VGKC subunits, or to the intracellular interacting proteins, but in many the targets remain undefined.
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