Differentiating central fever from infectious fever in intracerebral haemorrhage

In addition to infectious fever, stroke-related disturbances in thermoregulation, referred to as central fever, are frequently observed in patients with stroke, particularly in those with intracerebral haemorrhage (ICH). Rapid identification of the underlying cause of fever is crucial for treatment decisions. This study aims to identify clinical, laboratory and radiological parameters that differentiate central fever from infectious fever in patients with ICH.

We included 547 ICH patients in this retrospective, single-centre cohort study. Fever was defined as a body temperature exceeding 38.3°C for at least 2 consecutive days. Central fever was characterised by the absence of an infection diagnosis, cultured pathogens and any other identified cause of fever. CT scans were assessed visually and with a 3D nn-UNet for segmentation and subsequent quantification of all ICH components. Voxel-based lesion-symptom mapping was performed to identify lesion locations related to central fever. Univariate analyses and multiple logistic regression were conducted.

Fever occurred in 213 patients: 54 with central fever, 156 with infectious fever and 3 with other causes. Central fever was linked to higher scores on the National Institutes of Health Stroke Scale and worse outcomes (p<0.01). It had an earlier onset (median day 2 (1-3) vs 6 (4-9) p<0.01) and was more frequent in patients with lesions affecting the left midbrain and hypothalamic region (p<0.01). In contrast, infectious fever was associated with higher levels of infectious parameters (ie, C reactive protein, procalcitonin and leucocyte count). Its early onset (p<0.001) and affection of the left hypothalamic region (OR=9.7 (1.6 to 58.837), p=0.013) emerged as independent predictors of central fever.

Early onset and hypothalamic involvement are the strongest indicators of central fever, which may help guide evidence-based treatment decisions for patients with fever following ICH.