SummaryBackgroundResults of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.MethodsFOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.FindingsBetween Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months.InterpretationFluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.FundingUK Stroke Association and NIHR Health Technology Assessment Programme.

Listeria monocytogenes is the third most frequent cause of bacterial meningitis and has a predilection for elderly patients and the immunosuppressed. A small number of patients with Listeria monocytogenes meningoencephalitis have previously been reported to experience stroke-like symptoms that were attributed to microabscess formation and the mass effect of collections of infection in the brain. These infections led to temporary neurological deficits that resolved with antimicrobial treatment, rather than to true strokes with permanent neurological deficits. This report discusses the case of an 80- year-old male, who was immunosuppressed with mesalazine for the treatment of Crohn’s disease, and who went on to develop Listeria monocytogenes meningoencephalitis. 1 week into his admission, for antibiotic therapy, the patient began to experience new onset right upper limb weakness, nystagmus and past pointing. These symptoms were initially thought to be a complication of the infection. However, subsequent diffusion-weighted MRI revealed that the patient had more likely suffered an acute ischaemic event and a contrast-enhanced MRI performed later could not detect any abscess or large infective focus in a region that could explain the symptoms. This case report highlights the fact that ischaemic and infective pathologists may coexist in immunosuppressed Listeria patients and that clinical signs and symptoms should guide the use of appropriate imaging modalities such as MRI to clarify differentials so that ischaemia is not mistaken for the more common stroke mimic caused by infection in these patients.

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