Patient-Reported Disability Measures Do Not Correlate with Electrodiagnostic Severity in Carpal Tunnel Syndrome.

BACKGROUND: Electrophysiologic studies including electromyography and nerve conduction studies play a role in the evaluation of carpal tunnel syndrome (CTS), despite evidence that these studies do not correlate with CTS-specific symptom scores. There is a lack of evidence comparing electrophysiologic data with general measures of function. METHODS: Fifty patients presenting for CTS treatment over an 8-month period were analyzed retrospectively. All patients completed surveys including the Quick Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) and the Medical Outcomes Study 12-Item Short-Form Survey [(physical component summary 12, mental component summary (MCS-12)]. Electromyography and nerve conduction studies were performed on all patients and compared with outcome scores. RESULTS: Analysis demonstrated no relationship between DASH or MCS-12 and electrodiagnostic severity. No significant correlations were noted between DASH or MCS-12 and median motor or sensory latency. There was a moderate-weak correlation (rho = 0.34) between more severe electrophysiologic grade and better function based on physical component summary 12. CONCLUSIONS: Electrodiagnostic severity grades do not correlate with patient-reported disability, including the DASH and MCS-12 surveys. There is a counterintuitive correlation between more-severe electrodiagnostic findings and decreased physical disability. These findings indicate that disability may not correlate with electrodiagnostic severity of median neuropathy in CTS

High-resolution nerve ultrasound abnormalities in POEMS syndrome: a comparative study

Background: High-resolution nerve ultrasound (HRUS) has been proven to be a valuable tool in the diagnosis of immune-mediated neuropathies, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is an important differential diagnosis of CIDP. Until now, there have been no studies that could identify specific HRUS abnormalities in POEMS syndrome patients. Thus, the aim of this study was to assess possible changes and compare findings with CIDP patients. Methods: We retrospectively analyzed HRUS findings in three POEMS syndrome and ten CIDP patients by evaluating cross-sectional nerve area (CSA), echogenicity and additionally calculating ultrasound pattern scores (UPSA, UPSB, UPSC and UPSS) and homogeneity scores (HS). Results: CIDP patients showed greater CSA enlargement and higher UPSS (median 14 vs. 11), UPSA (median 11.5 vs. 8) and HS (median 5 vs. 3) compared with POEMS syndrome patients. However, every POEMS syndrome patient illustrated enlarged nerves exceeding reference values, which were not restricted to entrapment sites. In CIDP and POEMS syndrome, heterogeneous enlargement patterns could be identified, such as inhomogeneous, homogeneous and regional nerve enlargement. HRUS in CIDP patients visualized both increased and decreased echointensity, while POEMS syndrome patients pictured hypoechoic nerves with hyperechoic intraneural connective tissue. Discussion: This is the first study to demonstrate HRUS abnormalities in POEMS syndrome outside of common entrapment sites. Although nerve enlargement was more prominent in CIDP, POEMS syndrome patients revealed distinct echogenicity patterns, which might aid in its differentiation from CIDP. Future studies should consider HRUS and its possible role in determining diagnosis, prognosis and treatment response in POEMS syndrome

P2Y12 receptor modulation of ADP‐evoked intracellular Ca2+ signalling in THP‐1 human monocytic cells

Background and purpose: The Gi‐coupled, ADP‐activated P2Y12 receptor is well characterised as playing a key role in platelet activation via crosstalk with P2Y1 in ADP‐evoked intracellular Ca2+ response. There is limited knowledge on the role of P2Y12 in ADP‐evoked Ca2+ responses in other blood cells. Here we investigate the role of P2Y12 receptor activation in modulation of ADP‐evoked Ca2+ responses in human THP‐1 monocytic cells. Experimental approach: A combination of intracellular Ca2+ measurements, RT‐PCR, immunocytochemistry, leukocyte isolation and siRNA‐mediated gene knockdown were used to identify the role of P2Y12 receptor activation. Key results: ADP‐evoked intracellular Ca2+ responses (EC50 2.7 M) in THP‐1 cells were abolished by inhibition of phospholipase C (U73122) or sarco/endoplasmic reticulum Ca2+‐ATPase (thapsigargin). Loss of ADP‐evoked Ca2+ responses following treatment with MRS2578 (IC50 200 nM) revealed a major role for P2Y6 in mediating ADP‐evoked Ca2+ responses. ADP‐evoked responses were attenuated either with pertussis toxin treatment, or P2Y12 inhibition with two chemically distinct antagonists (ticagrelor, IC50 5.3 M; PSB‐0739, IC50 5.6 M). ADP‐evoked responses were suppressed following siRNA‐mediated P2Y12 gene knockdown. The inhibitory effects of P2Y12 antagonists were fully reversed following adenylate cyclase inhibition (SQ22536). P2Y12 receptor expression was confirmed in freshly isolated human CD14+ monocytes. Conclusion and implications: Taken together, these data suggest that P2Y12 activation positively regulates P2Y6‐mediated intracellular Ca2+ signalling through suppression of adenylate cyclase activity in human monocytic cells

Calcium-mediated actin reset (CaAR) mediates acute cell adaptations

Actin has well established functions in cellular morphogenesis. However, it is not well understood how the various actin assemblies in a cell are kept in a dynamic equilibrium, in particular when cells have to respond to acute signals. Here, we characterize a rapid and transient actin reset in response to increased intracellular calcium levels. Within seconds of calcium influx, the formin INF2 stimulates filament polymerization at the endoplasmic reticulum (ER), while cortical actin is disassembled. The reaction is then reversed within a few minutes. This Calcium-mediated actin reset (CaAR) occurs in a wide range of mammalian cell types and in response to many physiological cues. CaAR leads to transient immobilization of organelles, drives reorganization of actin during cell cortex repair, cell spreading and wound healing, and induces long-lasting changes in gene expression. Our findings suggest that CaAR acts as fundamental facilitator of cellular adaptations in response to acute signals and stress

Intercellular Calcium Signaling Induced by ATP Potentiates Macrophage Phagocytosis

Summary: Extracellular ATP is a signaling molecule exploited by the immune cells for both autocrine regulation and paracrine communication. By performing live calcium imaging experiments, we show that triggered mouse macrophages are able to propagate calcium signals to resting bystander cells by releasing ATP. ATP-based intercellular communication is mediated by P2X4 and P2X7 receptors and is a feature of pro-inflammatory macrophages. In terms of functional significance, ATP signaling is required for efficient phagocytosis of pathogen-derived molecules and apoptotic cells and may represent a target for macrophage regulation by CD39-expressing cells. These results highlight a cell-to-cell communication mechanism tuning innate immunity. : Exchange of information is critical for an efficient immune response. Here, Zumerle et al. show that macrophages exploit ATP release as a paracrine communication mechanism to propagate calcium signals to neighboring cells. Signal propagation relies on P2X4 and P2X7 receptors and sustains macrophage phagocytosis. Keywords: macrophage, adenosine triphosphate, calcium, phagocytosis, P2X receptor

Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection

Contact with HIV-1 envelope protein elicits release of ATP through pannexin-1 channels on target cells; by activating purinergic receptors and Pyk2 kinase in target cells, this extracellular ATP boosts HIV-1 infectivity