Response to Nordström C-H,“Rapid Selective Brain Cooling With PolarCap ® —A Commercial Delusion?” (DOI: 10.1089/neu.2022.0456)

To the Editor:

I read with great interest the comment by Dr. Nordström ¹ on our recent article “Shorter Recovery Time in Concussed Elite Ice Hockey Players by Early Head-and-Neck Cooling—A Clinical Trial,” published in the Journal of Neurotrauma by Dr. Al-Husseini and colleagues. Dr. Nordström is a well-known expert in the pathophysiology of traumatic brain injury (TBI), and his interest in our study is highly appreciated.

However, I have concerns about some of the comments provided in his Letter to the Editor ¹ for the following reasons. First, it has an “apples versus oranges” approach. The study by Poli and colleagues ² was used by Dr. Nordström to suggest that head-neck cooling is ineffective, or at least insufficient in resulting in a clinically relevant cerebral temperature decrease. However, in stark contrast to our study on concussed ice hockey players, the cited study ² used head-neck cooling in an intensive care unit setting aiming to reduce brain temperature in normothermic and intubated, mechanically ventilated, and deeply sedated patients with an ischemic or hemorrhagic stroke severe enough to warrant invasive intracranial pressure monitoring. The aim of our present study was not to induce hypothermia, it was to achieve rapid normalization of brain temperature, based on available data showing that core temperature is markedly elevated in ice hockey players. ³ Since the core temperature is elevated by strenuous exercise, the brain temperature is also elevated and is typically even higher than in the body. ^3,4 The suggestion in this Letter to the Editor that brain and core temperatures are similar lacks support from recent studies.

Further, in the cited study by Poli and colleagues, the Sovika^® cooling helmet was used, into which a gel at 4°C without active cooling was placed. Arguably, the cooling effect was likely transient. In contrast, we used a circulating fluid maintained at 0°C throughout the cooling treatment for a minimum of 45 min. In fact, using other head-neck cooling devices similar to ours, a 2°C decrease of cortical temperature monitored by an invasive sensor in severe stroke or TBI patients was achieved within 15 min after application of a cooling helmet, and could be maintained up to 2.5°C below core temperature for 48 h. ⁵ Based on theoretical modeling, ⁶ a head cap may lower the temperature in superficial cortical regions, while to cool deep brain structures, neck cooling may also be needed. ^5,7 Such data argue that a combination of head and neck cooling has the potential to lower brain temperature, in our study aimed at attenuating exercise-induced hyperthermia at time of concussion.

Dr. Nordström also argues that there is no solid proof that the our selective head-neck cooling method actually lowers brain temperature (and metabolism). My second concern is based on the concept in science that “absence of evidence of a certain mechanism is not evidence of absence for that mechanism.” I agree with Dr. Norström that any results obtained by the zero-heat flux method used in our previous report ⁸ must be interpreted with much caution with regard to the uncertainties of the depth of measurements (typically stated to be 1-2 cm below the surface of the skin), and it is debated if superficial cerebral temperature can at all be assessed with this method. However, as mentioned, there are other reports showing a reduction in superficial cortex by invasive monitoring or tympanic membrane measurements using similar methods of head-neck cooling. ^5,7,9

While invasive intracranial temperature monitoring in hyperthermic elite athletes would solve this issue, it is unrealistic due to the obvious ethical and practical limitations. The use of magnetic resonance imaging is an alternative, ¹⁰ although it requires interruption of the cooling and may not be feasible. Another approach could be to measure the indirect biological effects of selective head-neck cooling on biomarkers of neuronal and glial injury in groups of athletes concussed at strenuous exercise. Such studies are ongoing by our group.

Dr. Nordström claims that the observed effects achieved by cooling are merely “a delusion.” This is an unnecessarily harsh choice of wording that requires some comments. For many treatments of neurosurgical and neurological disorders, the mechanisms explaining efficacy are often unknown. That list can be long, but just to mention a few: Do we really know in detail, for example, how nimodipin used in subarachnoid hemorrhage or common antiepileptic drugs work, or for that matter, lithium or electroconvulsive therapy for psychiatric disorders? Are these treatments then merely “delusional” and should be discarded?

It has been shown beyond reasonable doubt that hyperthermia exacerbates the extent of acute brain injuries. However, we may agree that the biological mechanisms of head-neck cooling may be multi-faceted and extend beyond temperature effects. Therapeutic efficacy and changes in cerebral blood flow have indeed been observed beyond the acute post-concussive period, ^11,12 findings that cannot be explained merely by attenuation of cerebral hyperthermia.

Again, we thank Dr. Nordström for his insightful comments on our study. ¹³ We hope our work provides a basis for improved therapies in the acute post-concussive setting and inspires further studies on the role of temperature, and cooling, in sport-related concussion.