Clinical, radiological and immunological features predictive of relapse after a 1st episode of CNS inflammatory demyelination in Australian children

Background: The risk of multiple sclerosis (MS) is dependent on multiple variables. The risk of MS in Australian children differs from children living in the northern hemisphere. Early recognition and treatment of MS in children is important. Anti-Myelin oligodendrocyte glycoprotein (MOG) antibodies may define a subtype of central nervous system demyelination. Method: Using multivariate analysis, we determined the clinical and MRI features predictive of MS in 88 children from New South Wales, Australia, with a first demyelinating event and minimum 1 year follow-up. We tested the McDonald, KIDMUS, Callen and Verhey MRI MS criteria. 73/88 children were tested for anti-MOG antibodies. A comparison was made to determine if a clinical sub-type was definable. Results: After a mean of 5.2 years 13/88 (15%) of children had MS. A preceding infection was protective and corpus callosal lesions, the presence of both well and poorly demarcated lesions, and contrast-enhancing lesions were predictive of MS. The respective sensitivity and specificity of the MRI MS criteria were McDonald 2005 (69%, 68%), McDonald 2010 (58%, 95%), KIDMUS (8%, 100%), Callen (69%, 85%) and Verhey (62%, 84%) and for McDonald 2010 criteria applied to baseline and serial scans, 91% and 93%. MOG antibody positive patients were younger, had a raised erythrocyte sedimentation rate, a monophasic (86%) course and recurrent (75%) optic neuritis. Conclusion: The risk of MS appears lower in New South Wales children compared to international cohorts. The McDonald 2010 criteria performed well except in those with encephalopathy. Anti-MOG antibodies were more common in young children with ADEM and bilateral optic neuritis. The pathogenicity and therapeutic implications of anti-MOG antibodies needs further study

Semantic Integration of Cervical Cancer Data Repositories to Facilitate Multicenter Association Studies: The ASSIST Approach

The current work addresses the unifi cation of Electronic Health Records related to cervical cancer into a single medical knowledge source, in the context of the EU-funded ASSIST research project. The project aims to facilitate the research for cervical precancer and cancer through a system that virtually unifi es multiple patient record repositories, physically located in different medical centers/hospitals, thus, increasing fl exibility by allowing the formation of study groups “on demand” and by recycling patient records in new studies. To this end, ASSIST uses semantic technologies to translate all medical entities (such as patient examination results, history, habits, genetic profi le) and represent them in a common form, encoded in the ASSIST Cervical Cancer Ontology. The current paper presents the knowledge elicitation approach followed, towards the defi nition and representation of the disease’s medical concepts and rules that constitute the basis for the ASSIST Cervical Cancer Ontology. The proposed approach constitutes a paradigm for semantic integration of heterogeneous clinical data that may be applicable to other biomedical application domains

Semantic Integration of Cervical Cancer Data Repositories to Facilitate Multicenter Association Studies: The ASSIST Approach

The current work addresses the unification of Electronic Health Records related to cervical cancer into a single medical knowledge source, in the context of the EU-funded ASSIST research project. The project aims to facilitate the research for cervical precancer and cancer through a system that virtually unifies multiple patient record repositories, physically located in different medical centers/hospitals, thus, increasing flexibility by allowing the formation of study groups “on demand” and by recycling patient records in new studies. To this end, ASSIST uses semantic technologies to translate all medical entities (such as patient examination results, history, habits, genetic profile) and represent them in a common form, encoded in the ASSIST Cervical Cancer Ontology. The current paper presents the knowledge elicitation approach followed, towards the definition and representation of the disease’s medical concepts and rules that constitute the basis for the ASSIST Cervical Cancer Ontology. The proposed approach constitutes a paradigm for semantic integration of heterogeneous clinical data that may be applicable to other biomedical application domains

Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination.

Abstract OBJECTIVE: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. METHODS: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. RESULTS: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10\u2009mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of 652 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077). CONCLUSION: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation

The so-called "Athonite" type of church and two shrines of the Theotokos in Constantinople

The textual descriptions of alterations carried in the two most important Theotokos churches in Constantinople, the Blachernae and the Theotokos in Chalkoprateia, locus on the addition of lateral apses to the buildings. This type is very likely the source of influence and also the basis for the transference of the concept of lateral apses in Athonite katholika

Un palais paléologue à Thessalonique

La donation d’un domaine incluant une résidence noble à un couvent de femmes par Anne de Savoie et plus tard à un monastère par Manuel II, constitue le point de départ d’un réexamen de certaines caractéristiques de la topographie urbaine de Thessalonique au xive siècle. Les spécificités de l’architecture et de l’histoire de l’église connue sous le nom du « Prophète Élie » sont liées aux évènements relatifs à la fin de la controverse hésychaste et à la suprématie définitive de la maison des Paléologues sur les Cantacuzènes. L’église est identifiée au katholikon des Saints-Anargyres et sa construction attribuée à Anne. La donation par Anne au couvent des Saints-Anargyres incluait la noble résidence de Guy de Lusignan, où elle résida probablement en tant que nonne Anastasie. Cette propriété convoitée devint un sujet de conflit et son histoire révèle à quel point le paysage urbain de Thessalonique reflète les relations complexes d’une société multiethnique et très diversifiée. Il se peut cependant qu’il ne soit que l’un des nombreux palais paléologues de la ville.A Palaiologan palace in Thessaloniki The donation of land property, including a noble residence, to a nunnery, by Anna of Savoy and later to a convent by Manuel II, becomes the starting point for reevaluating certain features of the urban topography of 14th c. Thessaloniki. The peculiarities in the architecture and history of the church known as « Prophetes Helias » are connected to events relating to the end of the hesychastic controversy and the final prevalence of the house of Palaiologoi against the Cantacuzenoi. The church is identified with the katholikon of the Hagioi Anargyroi and its construction attributed to Anna. The donation by Anna to the nunnery of the Hagioi Anargyroi included the noble residence of Guy de Lusignan, where probably she resided as the nun Anastasia. This prised property became a subject of contention and its history reveals aspects of the way Thessaloniki’s cityscape reflected the complex relations of a multiethnic and highly diverse society. Therefore it might just be one of several Palaiologan palaces in the city

The church of prophetes Elias in Thessaloniki, Anna of Savoy and the so-called "Avle tou Syrge"

 The article reexamines certain architectural peculiarities of the church known as Prophetes Elias. These are examined in conjunction with other historic details of 14th century Thessaloniki to develop a new proposal for its iden­tification.The building stands apart from other surviving churches of Palaeologan Thessaloniki, because of its size, its prominent location, its typology (being a triconch variation known for its Athonite connotations) and also its gallery.Its size and location speak of a possible imperial foundation. This is further corroborated because in its neighbourhood was also located the Ottoman administrator’s residence (konaki) and the area was known pos­sibly as balaat (relating to a palatial residence). Moreover the church, when turned into a mosque, was called sarayli camii (palace mosque), possibly continuing a late Byzantine arrangement. The gallery itself indicates a possible connection to a female member of the royal family since there is such a trend in women-funded monasteries in Constantinople at least from the Komnenian period. And still the choice of the Athonite architectural type might be an indication of Thessaloniki’s special affiliation to the monastic community in Chalkidiki.Bringing all these together the possibility that the church is the result of Anna Palaeologina’s (Anna of Savoy) patronage is reexamined since her connection to the city and her activity there are well attested from other sources: she became the nun Anastasia, praised by the Athonite community for her role in the hesychast controversy, and she was often visited by monks in her “God-guarded palace”. She established Gregory Palamas (a former Lavra abbot) as the city’s archbishop and she made a donation to the nunnery of Hagioi Anargyroi including a large estate comprising of a residence among other lots. This is the most interesting piece of information since the property in question was a prized one (judging from its continual change of hands) and known as the one belonging to Syrge (Guy de Luzignan) later King of Armenia.Therefore, in order to tie all these and make some sense out of the scat­tered information it is proposed that the church known as Prophetes Elias might have been the Katholikon of Hagioi Anargyroi nunnery where Anna/Anastasia ended her days as a nun residing in the so-called Avle tou Syrge her “God-guarded palace” nearby. That is why the church became known later as the “palace mosque” while its neighbourhood had a similar name. Apparently Nea Mone built later in the vicinity of former palaces, was also nearby and thus the transference of the Avle tou Syrge to the monastery is explained as well as is its reclaiming issued by the nuns of Hagioi Anar­gyroi.What we come up with, beyond the interesting suggestion, is a fresh way to look at Byzantine architecture while trying to explain the peculiarities of an impressive monument.

From Town to Countryside: Middle-Byzantine Bath-Houses in Eastern Crete and Their Changing Functions

The article examines the context of a recently discovered double bath-house complex in Loutres, a site near Mochlos on the north shore of eastern Crete. The excavators explore the broader questions posed by the finding, in connection to both its immediate surroundings and its wider periphery. Its relation to the site&rsquo;s geography, a ravine on the shore, forms the starting point to address issues regarding its original use as well as its later transformations. The enquiry leads into considering similar structures with different fates in the area and the connotations regarding their relationship to both the landscape and the settlements to which they belonged. The article goes on to discuss the general issues of the historic context of medieval Crete concerning both the archaeology and the information from the sources. It seems that long-held concepts about the abandonment of seaside settlements due to the so-called &ldquo;Arab threat&rdquo; are no longer valid. On the contrary, archaeology proves the continuity of the settlements of eastern Crete, both in Loutres and elsewhere. Moreover, the later use of the bath-houses in the area provides evidence for social changes after the 13th century impacting on both the landscape and its settlements

Cerebrospinal fluid B-cell expansion in longitudinally extensive transverse myelitis associated with neuromyelitis optica immunoglobulin G

A first episode of central nervous system (CNS) demyelination may represent heterogeneous entities such as acute disseminated encephalomyelitis, clinically isolated syndrome, neuromyelitis optica (NMO), or multiple sclerosis. As new immune therapies become available, it is increasingly important to make an early diagnosis. Autoantibodies such as NMO immunoglobulin G (IgG) and myelin oligodendrocyte glycoprotein IgG are increasingly being employed to define subgroups of CNS demyelination or guide treatment. Similarly, cerebrospinal fluid (CSF) immunophenotyping can demonstrate B-lymphocyte subpopulation expansion, which has been used to guide therapy in other autoimmune CNS disorders. We present a report on a 15-year-old male with longitudinally extensive transverse myelitis with magnetic resonance imaging findings of oedema, cavitation, and gadolinium enhancement. NMO-IgG and aquaporin 4 IgG were positive; thus, we diagnosed a limited form of NMO. Acute CSF immunophenotyping revealed a 3.6% expansion of CD19 B-cell populations, whereas a comparison group of five children (4 males, age range 2–15y; mean age 7y) with other neurological disorders showed only a 0.51% expansion (SD 0.25%). In view of the diagnosis of a 'limited form of neuromyelitis optica', we therefore elected to treat him aggressively from the outset with a prolonged steroid regimen and mycophenylate mofetil. This case demonstrates a correlation between autoantibody production and CSF B lymphocyte expansion in an individual with CNS demyelination. These approaches could be used in individuals with a first episode of CNS demyelination to help delineate immunological subgroups and guide treatment.5 page(s