Reconsidering Rigidity in the Diagnosis of Neuroleptic Malignant Syndrome: A Case Report.

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal syndrome classically encountered in patients receiving typical antipsychotic agents. However, many physicians have also reported the occurrence of NMS with atypical antipsychotics, notably with atypical presentations. In this report, we present a case in which a patient's antipsychotic regimen during a psychotic episode (which involved both typical and atypical antipsychotics) subsequently led to NMS. During his stay, the patient developed an altered level of consciousness, elevation of creatine phosphokinase, hemodynamic instability, and a fever. However, the patient did not have signs of rigidity, the cardinal sign of this syndrome. The authors concluded that patients could develop NMS without rigidity while receiving an antipsychotic. Given this presentation, the authors suggest that clinicians have a high level of suspicion for NMS to avoid misdiagnosis and subsequent adverse consequences. Hence, clinicians must be vigilant about atypical presentations of NMS without rigidity.

Characterising the inhibitory actions of ceramide upon insulin signaling in different skeletal muscle cell models: a mechanistic insight.

Ceramides are known to promote insulin resistance in a number of metabolically important tissues including skeletal muscle, the predominant site of insulin-stimulated glucose disposal. Depending on cell type, these lipid intermediates have been shown to inhibit protein kinase B (PKB/Akt), a key mediator of the metabolic actions of insulin, via two distinct pathways: one involving the action of atypical protein kinase C (aPKC) isoforms, and the second dependent on protein phosphatase-2A (PP2A). The main aim of this study was to explore the mechanisms by which ceramide inhibits PKB/Akt in three different skeletal muscle-derived cell culture models; rat L6 myotubes, mouse C2C12 myotubes and primary human skeletal muscle cells. Our findings indicate that the mechanism by which ceramide acts to repress PKB/Akt is related to the myocellular abundance of caveolin-enriched domains (CEM) present at the plasma membrane. Here, we show that ceramide-enriched-CEMs are markedly more abundant in L6 myotubes compared to C2C12 myotubes, consistent with their previously reported role in coordinating aPKC-directed repression of PKB/Akt in L6 muscle cells. In contrast, a PP2A-dependent pathway predominantly mediates ceramide-induced inhibition of PKB/Akt in C2C12 myotubes. In addition, we demonstrate for the first time that ceramide engages an aPKC-dependent pathway to suppress insulin-induced PKB/Akt activation in palmitate-treated cultured human muscle cells as well as in muscle cells from diabetic patients. Collectively, this work identifies key mechanistic differences, which may be linked to variations in plasma membrane composition, underlying the insulin-desensitising effects of ceramide in different skeletal muscle cell models that are extensively used in signal transduction and metabolic studies.