Primary stabbing headache in children and adolescents.

AIM: To examine the characteristics of primary stabbing headache (PSH) in typically developing children and adolescents. METHOD: In this prospective non-interventional hospital-based study, we examined 42 eligible individuals (24 females, 18 males; 26 white; mean age 12y 1mo, range 6y-16y 1mo) with spontaneous transient stabs. A headache focused history and/or a headache diary was obtained from each patient. All patients had normal neurological examination. Diagnosis of primary headache was based on the International Classification of Headache Disorders, Third Edition (ICHD-3) beta version. RESULTS: Duration of stabs ranged from a few seconds to up to 10 minutes. Stabs were located in a variety of sites on the cranium but mostly in the extra-trigeminal regions (n=28). Intensity of stabs varied from moderate (n=4) to severe (n=38). The frequency of the stabs ranged from daily to monthly. There were up to 50 stabs per headache attack. Stabs among our patients occurred independently from those caused by other primary headache types. Accompanying symptoms during stabs were reported by eight patients. Family history of primary headaches was identified (n=17). Familial transmission of PSH was recognized among two patients. All patients had normal brain magnetic resonance imaging. INTERPRETATION: The presentation and nature of PSH in children and adolescents varies widely. PSH in children may be a different entity to that in adults, and there is a need for further research to support changes in the ICHD-3 criteria for PSH in children and adolescents. WHAT THIS PAPER ADDS: Presentation of childhood primary stabbing headache (PSH) varies widely. Duration of PSH could last from a few seconds up to 10 minutes.

FASN activity is important for the initial stages of the induction of senescence.

Senescent cells accumulate in several tissues during ageing and contribute to several pathological processes such as ageing and cancer. Senescence induction is a complex process not well defined yet and is characterized by a series of molecular changes acquired after an initial growth arrest. We found that fatty acid synthase (FASN) levels increase during the induction of senescence in mouse hepatic stellate cells and human primary fibroblasts. Importantly, we also observed a significant increase in FASN levels during ageing in mouse liver tissues. To probe the central role of FASN in senescence induction, we used a small-molecule inhibitor of FASN activity, C75. We found that C75 treatment prevented the induction of senescence in mouse and human senescent cells. Importantly, C75 also reduced the expression of the signature SASP factors interleukin 1α (IL-1α), IL-1ß and IL-6, and suppressed the secretion of small extracellular vesicles. These findings were confirmed using a shRNA targeting FASN. In addition, we find that FASN inhibition induces metabolic changes in senescent cells. Our work underscores the importance of C75 as a pharmacological inhibitor for reducing the impact of senescent cell accumulation.