Tony Gardner-Medwin

© 2015 Elsevier Inc.Brain biopsies have an uncertain role in the diagnosis of patients with dementia or neurologic decline of unknown etiology. They are often performed only after an exhaustive panel of less invasive tests and procedures have failed to provide a definitive diagnosis. The objective of this study was to evaluate the sensitivity of brain biopsies in this patient group through the retrospective analysis of 53 brain biopsies performed for neurologic disease of unknown etiology at a single tertiary care institution between December 2001 and December 2011. Patients with known nonlymphomatous neoplasms thought to be associated with the neurologic symptoms or with immunodeficiency were excluded from the study. Furthermore, the clinical presentation, imaging and laboratory tests were compared between diagnostic groups to identify factors more likely to yield a diagnosis. Sixty percent of the biopsies were diagnostic, with the most common histologic diagnosis of central nervous system lymphoma in 14 of 53 patients followed by infarct in four subjects. A few patients were found to have rare and unsuspected diseases such as lymphomatosis cerebri, neurosarcoidosis and neuroaxonal leukodystrophy. Complications from biopsy were uncommon and included hemorrhage and infection with abscess formation at the biopsy site. These results suggest that brain biopsies may be useful in difficult cases in which less invasive measures have been unable to yield a definitive diagnosis.

The use of evidence to resolve uncertainties is key to many endeavours, most conspicuously science and law. Despite this, the logic of uncertainty is seldom taught explicitly, and often seems misunderstood. Traditional educational practice even fails to encourage students to identify uncertainty when they express knowledge, though mark schemes that reward the identification of reliable and uncertain responses have long been shown to encourage more insightful understanding. In our information-rich society the ability to identify uncertainty is often more important than the possession of knowledge itself. In both science and law there are fundamentally different kinds of uncertainty at issue. There is uncertainty whether a particular hypothesis is correct, and there is uncertainty about observable data that may be generated if a particular hypothesis is correct. Both are expressed in terms of probabilities. Each has its own domain of application and its own logic, but the inter-relationship is complex and sometimes misunderstood. Hypothesis probabilities are always open to error through possible failure to take account of realistic alternatives, while the proper inferences that can be drawn from data probabilities (often in the context of significance testing) are quite limited and easily over-interpreted. When considering these two kinds of probability in a court of law it is possible to interpret the phrase 'reasonable doubt' in different ways. It can be seen as addressing data uncertainty: whether such incriminating evidence might with reasonable probability arise to confront an innocent person. Or (the more conventional view) it can be seen as some sort of threshold level on the probability that the defendant is guilty (a hypothesis probability). Each typically involves elements of subjective judgement, but fewer issues and uncertainties arise when considering the data probability and it is argued that this is often the more critical and proper issue for a jury to address. This has particular repercussions for cases involving identification of a suspect through trawl of a DNA or other database.