A middle-aged man with palmoplantar keratoderma (see Vignette 83) and who had a cadavaric renal transplant overseas 5 years ago presented with generalized tonic-clonic seizures followed by impaired consciousness. He subsequently recovered with full consciousness, and reported worsening headaches over the past week. Clinical examination showed that he was febrile at 38.4 degrees Celsius, but no focal neurological deficits were found.

CT head showed oedema around the right occipital lobe, which a subsequent MRI of the brain revealed as surrounding a solid 1.1 cm nodule. Emergency surgery was offered by the neurosurgeon, who had 2 questions over the phone (and I add a third):


  1. What would be the optimal empirical antimicrobial therapy?
  2. What should intra-operative specimens be sent for?
  3. What are the most likely differential diagnoses?

[Updated 24th June 2018]

This is an immunocompromised patient – a careful history should be taken to ascertain the nett state of immunosuppression – and therefore the differential list is very wide for a solitary nodule in the brain with surrounding edema and inflammation. This ranges from pyogenic brain abscess to brain infection/abscess caused by opportunistic pathogens such as Nocardia spp., fungi for which the most common would be Aspergillus spp. and Cryptococcus spp. (forming a cryptococcoma), Mycobacterium tuberculosis, and non-infectious causes such as lymphoma.

Therefore intra-operative specimens should be sent for diagnostic testing targeting this broad range of differential diagnoses – there is no real short cut at this current state. However, it is unnecessary to provide empirical antimicrobial therapy that targets all the infectious causes listed, especially if the laboratory turnaround time is relatively rapid (i.e. within a few days). The majority of non-pyogenic infections do not result in rapid, irreversible clinical deterioration, particularly if surgery to remove the foci has been performed, and a “kitchen sink” prescription of antimicrobial agents greatly increases the risk of drug adverse effects and interactions.

There are scenarios in clinical practice where the neurosurgeon is reluctant to operate even if the nodule is surgically easily accessible(which is substantially more common in the public as opposed to private sector), or where the lesion is in an inaccessible part of the brain. These are far more complex: the neurosurgical team must be persuaded in the first instance, while in the second, obtaining CSF for testing should be attempted although the sensitivity is far lower for the purposes of making a diagnosis.