We read with great interest the study by Lim et al, 1 which aimed to develop an easily applicable scale to grade the severity of autoimmune encephalitis (AE). Nine key clinical features were identified and included in the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). CASE showed good interobserver and intraobserver reliability, and internal consistency, as well as a high correlation with the modified Rankin Scale (mRS).We applied CASE retrospectively to a cohort of 60 patients with AE, admitted to our institution between 2012 and 2018, and prospectively in 3 additional patients. Median age at onset was 55 years (range = 3 months-88 years), in 13 of 63 (21%) onset was before 18 years of age, and 34 of 63 (54%) were female. All patients fulfilled the clinical diagnostic criteria for AE 2 : definite AE was diagnosed in 16 of 63 patients (25%), definite anti-NMDA receptor encephalitis in 11 of 63 (17%), definite autoimmune limbic encephalitis in 6 of 63 (10%), antibody-negative probable AE in 4 of 63 (6 %), possible AE in 25 of 63 (40%), and Hashimoto encephalopathy in 1 of 63 (2%). At the disease nadir, median mRS score was 4 (range = 3-5). We applied CASE at maximum clinical severity (median CASE score = 9, range = 3-24). In our cohort, CASE significantly correlated with mRS (p < 0.0001, r 2 = 0.5025; Fig), although the correlation strength was weaker than that reported by Lim et al. However, we encountered several issues when CASE was applied to our patients that need to be clarified. Severe clinical conditions, such as coma and status epilepticus, make other items hardly assessable (eg, gait instability, language). In such cases, it is not specified what score should be given to items that are not directly assessable (we gave the maximum score). Postictal state after seizures also interferes with the evaluation of most items. The authors should clarify how to apply the scale in these situations and whether this score is meant to be used only in clinically stable patients. Furthermore, when applying CASE to a pediatric population, some items, such as memory and language, were not easily assessable. We think that the scale is more suitable for adult patients. Moreover, it would be appropriate to develop a different scale for patients with altered consciousness.CASE is potentially a useful tool and addresses the unmet need of clinical scales to grade AE severity, as mRS is quite coarse in evaluating this condition. However, CASE needs further improvement and validation to be employed in clinical trials.

No abstract

Podoplanin (Pdpn) is a mucin-type transmembrane protein that has been implicated in multiple physiological settings including lymphangiogenesis, platelet aggregation, and cancer metastasis. Here, we reported an absence of Pdpn transcript expression in the resting mouse monocytic macrophages, RAW264.7 cells; intriguingly, a substantial upregulation of Pdpn was observed in activated macrophages following Helicobacter pylori or lipopolysaccharide stimulation. Pdpn-knockout macrophages demonstrated intact phagocytic and intracellular bactericidal activities comparable to wild type but exhibited impaired migration due to attenuated filopodia formation. In contrast, an ectopic expression of Pdpn augmented filopodia protrusion in activated macrophages. NanoString analysis uncovered a close dependency of Filamin C gene on the presence of Pdpn, highlighting an involvement of Filamin C in modulation of actin polymerization activity, which controls cell filopodia formation and migration. In addition, interleukin-1β production was significantly declined in the absence of Pdpn, suggesting a role of Pdpn in orchestrating inflammation during H. pylori infection besides cellular migration. Together, our findings unravel the Pdpn network that modulates movement of active macrophages.

No abstract

No abstract

Helicobacter pylori is well established as a causative agent for gastritis, peptic ulcer, and gastric cancer. Armed with various inimitable virulence factors, this Gram-negative bacterium is one of few microorganisms that is capable of circumventing the harsh environment of the stomach. The unique spiral structure, flagella, and outer membrane proteins accelerate H. pylori movement within the viscous gastric mucosal layers while facilitating its attachment to the epithelial cells. Furthermore, secretion of urease from H. pylori eases the acidic pH within the stomach, thus creating a niche for bacteria survival and replication. Upon gaining a foothold in the gastric epithelial lining, bacterial protein CagA is injected into host cells through a type IV secretion system (T4SS), which together with VacA, damage the gastric epithelial cells. H. pylori does not only establishes colonization in the stomach, but also manipulates the host immune system to permit long-term persistence. Prolonged H. pylori infection causes chronic inflammation that precedes gastric cancer. The current review provides a brief outlook on H. pylori survival tactics, bacterial-host interaction and their importance in therapeutic intervention as well as vaccine development.

In December 2017, 79 delegates attended the 2nd regional plasmapheresis conference and workshop for Southeast Asia (SEA) on the immunomodulatory role of plasma exchange in central and peripheral nervous system disorders in Kuala Lumpur, Malaysia. This meeting featured 6 plenary lectures, interactive sessions dedicated for experience sharing, case presentations, and a practical session for paramedics. Clinical experts and researchers from 7 SEA countries and India shared experience and challenges in treating autoimmune neurological disorders. While the spectrum of diseases and neurology practice remained largely similar, there was great disparities in accessibility of therapeutic plasma exchange (TPE) within SEA countries and between urban or rural settings. Costs, human resources, and healthcare policies are common challenges in providing sustainable TPE services. Novel techniques and innovative ideas in performing TPE were explored. A working consortium comprising of key opinion leaders was proposed to improve standards of TPE and enhance future research.

No abstract