In patients with ischemic stroke, tympanic temperature was not elevated on admission even in patients with more severe strokes (TACS), and admission temperature did not correlate with admission NIHSS. Instead, we found that peak temperature, occurring at around 1.5 to 2 days after stroke and overall temperature, as expressed by AUC were associated with admission stroke severity as measured by NIHSS and TACS subtype. Peak temperatures were higher, occurred later and temperature elevation lasted longer in more severe than less severe strokes perhaps indicating a more prolonged, greater inflammatory response to the volume of infarcted tissue. Patients with poor functional outcome (mRS≥3) at 90 days had higher admission and peak temperatures than patients with good outcome (mRS≤2), although all admission temperatures were <37°C. We were not able to find a source of infection in 69% of pyrexial patients, and no alternative cause of pyrexia, other than the stroke itself, in 44%.
This prospective study of detailed four-hourly tympanic temperature measurements up to five days after ischemic stroke helps explain the varying results of previous studies (Tables 1 and 2) some of which found associations between admission temperature, stroke severity and outcome [3, 4, 6, 12, 13], while others did not [8, 14, 16, 19]. This variation can be attributed to some studies being retrospective, or not specifying the timing of temperature recording after stroke, sampling temperature only once, measuring “admission” temperature relatively late after stroke, only measuring serial temperature up to 72 hours, the different severities of stroke included in each study or including patients with both haemorrhagic and ischemic stroke. Consistent with our results, others showed that patients with more severe strokes experience higher peak temperatures , and that elevated temperature at 24 hours [14, 17, 19], 48 hours  or 7 days  after stroke was more closely linked to poor outcome than admission readings. Our detailed longitudinal findings also demonstrate the higher, later and longer duration of temperature elevation in more severe than less severe stroke, which perhaps has not been appreciated previously.
Our study has limitations. The small sample size was constrained by selection of patients for an MR imaging study, but on the other hand it allowed very detailed temperature monitoring. However, the range of stroke severity was consistent with those that would be considered for trials of therapeutic hypothermia. A larger sample size would allow more adjustment for potential confounders, and clarification of the significance of any differences in timing of peak temperature readings, and comparison of patients whose tympanic temperature may have been affected by antibiotics and antipyretics, although our results show that pyrexia was just as common in patients who were prescribed paracetamol as in those who were not, in contrast to others’ results . However paracetamol may have influenced the profile of temperature change. Although our data on temperature profile and stroke severity are consistent with five previous studies, we cannot exclude the possibility of an association between admission temperature and stroke severity. The study strengths are the detailed four-hourly tympanic temperature measurements for 120 hours after ischemic stroke and the detailed comparison with stroke subtype, severity and outcome. The duration of temperature recording ensured that the peak temperature was captured in both TACS and non-TACS.
Two other points raise questions for further study. Admission temperature in the patients with more severe strokes, ie TACS, was not higher than in patients with milder strokes, as might have been expected. Perhaps, by analogy with other serious acute illness, the temperature in severe stroke may reflect severe illness . Secondly, why do patients with a poor outcome have a marginally higher (but still normothermic) admission temperature, and while severe stroke is associated with poor outcome, severe stroke is not associated with admission temperature? This might be explained at least in part by a possible cascade of events suggested in experimental data. Increased temperature opens the blood–brain barrier  which, in acute ischemia, would lead to increased extracellular oedema, more infarct swelling, more restricted capillary flow in the ischemic tissue, less chance of reperfusion, all contributing to increasing ischemic damage, swelling and leading to a larger infarct around 48 hours , consolidating the potential for tissue damage that was suggested by the severe stroke symptoms at presentation, and consequently leading to the poor outcome at 90 days. Longer duration of temperature monitoring should be considered in future research to improve understanding of temperature profiles after stroke.
This interpretation, if true, raises some implications for therapeutic hypothermia trials. Firstly, and paradoxically, patients may benefit the most from hypothermia if it prevents the tissue cascade outlined above from causing more tissue damage and should certainly not be excluded from trials; thus cooling should be initiated as early as possible and not influenced by the patient’s admission temperature. However cooling may only prevent worsening of damage, not actively salvage tissue that is already at risk, so combinations of therapies to salvage (e.g. thrombolysis) as well as to restrict progressive new damage (e.g. hypothermia, if it works) may be required. Secondly, if the main effect of hypothermia is to reduce blood–brain barrier opening thus preventing the cascade that leads to larger stroke lesions, then hypothermia could still be valuable if started many hours after the stroke when the possibility of salvaging at risk tissue was lost but there was still some “future secondary damage” to prevent. If correct, then hypothermia should reduce subacute infarct oedema and mass effect. Thirdly, if correct, then therapeutic thrombolysis and hypothermia should work synergistically to produce greater benefit than either alone. However hypothermia may also have some disadvantages. In addition to increased risk of secondary infection and the need to manage unpleasant side effects like shivering, lower temperatures might delay thrombus lysis which pyrexia might accelerate. The balance of risk and benefit presented by these possibilities requires testing in future therapeutic trials of hypothermia after stroke.