Recognising uncertainty is important in clinical practice, given the multiple levels of uncertainty around diagnosis, investigation and treatment. In clinical practice, the exact diagnosis can be uncertain. For example, do we know if a patient’s stroke is atheromatous, thromboembolic or has a rarer cause? In this issue, Robert Hurford et al help us disentangle the rarer causes of strokes, and how to recognise and investigate them (page 35). And given that almost all patients with cramps have no significant underlying disease, how can we recognise those that do? Jildou Dijkstra et al provide some answers to this on page 23.

There is often uncertainty over the best ways to investigate patients, particularly as newer tests become available. Katherine Shon and Patrick Chinnery propose a step change in investigation—moving directly to whole gene sequencing (page 2)—thereby rapidly diagnosing mitochondrial cytopathies. …