Chronic Migraine May Be Associated With Postprandial Hypoglycemia in Adult Men: A Case Series.

Migraine is a common neurological disorder that significantly impacts patients around the world. In the United States, one in six individuals suffers from a migraine disorder. Despite its high prevalence, the etiology of migraine is not well understood. Multiple factors likely contribute to the development of both acute and chronic migraine, making the consensus as to the cause and treatment difficult. Presented here are three case studies involving adult males suffering from chronic migraine. Each subject provided a medical history and underwent physical, psychological, and neurological examinations. In addition, relevant bloodwork and cervical spine X-rays were obtained. Physical examination, laboratory studies, imaging, and psychological metrics were unremarkable with the notable exception of the three-hour oral glucose tolerance tests. All three patients displayed hypoglycemia at three hours. Furthermore, their symptoms markedly improved with the initiation of a ketogenic diet. These data are suggestive of a potential link between postprandial hypoglycemia and chronic migraine. Despite the small sample size, we feel that this report presents possible evidence for a connection between postprandial hypoglycemia and chronic migraine. Furthermore, properly controlled studies of larger sample sizes are required, but we suggest that clinicians consider screening patients for this easily overlooked metabolic disturbance, especially in the absence of other options.

CD4 Inhibits Helper T Cell Activation at Lower Affinity Threshold for Full-Length T Cell Receptors Than Single Chain Signaling Constructs.

CD4+ T cells are crucial for effective repression and elimination of cancer cells. Despite a paucity of CD4+ T cell receptor (TCR) clinical studies, CD4+ T cells are primed to become important therapeutics as they help circumvent tumor antigen escape and guide multifactorial immune responses. However, because CD8+ T cells directly kill tumor cells, most research has focused on the attributes of CD8+ TCRs. Less is known about how TCR affinity and CD4 expression affect CD4+ T cell activation in full length TCR (flTCR) and TCR single chain signaling (TCR-SCS) formats. Here, we generated an affinity panel of TCRs from CD4+ T cells and expressed them in flTCR and three TCR-SCS formats modeled after chimeric antigen receptors (CARs) to understand the contributions of TCR-pMHCII affinity, TCR format, and coreceptor CD4 interactions on CD4+ T cell activation. Strikingly, the coreceptor CD4 inhibited intermediate and high affinity TCR-construct activation by Lck-dependent and -independent mechanisms. These inhibition mechanisms had unique affinity thresholds dependent on the TCR format. Intracellular construct formats affected the tetramer staining for each TCR as well as IL-2 production. IL-2 production was promoted by increased TCR-pMHCII affinity and the flTCR format. Thus, CD4+ T cell therapy development should consider TCR affinity, CD4 expression, and construct format.