Bernhard Naunyn, a German pathologist and contemporary of Cushing, made remarks claiming that Cushing neither cited him in Cushings research nor expanded on any of the results that he had found in his original experiments. Research directions
Although a lot of progress has been made since 1901 when Harvey Cushing first expanded knowledge of what is now known as the Cushing reflex, there are still many aspects of the research that remain to be seen. The exact pathogenesis of the disease remains undetermined. The possibility that intracranial pressure (ICP) may not be the sole cause of the Cushing reflex per se came from an occurrence of Cushing blood pressure response occurring before increased ICP. Some research observed symptoms of Cushing reflex, without the usual increased ICP and medullary anemia, suggesting other causes that still require research. Axial brain stem distortion could be the pathogenesis of Cushing reflex.The nature of receptors mediating the Cushing response is also unknown. Some research suggests the existence of intracranial baroreceptors to trigger specific Cushing baroreceptor reflex. Experiments by Schmidt and his fellow researchers showed that the Cushing reflex is directed by autonomic nervous system, since its physiological change has to do with the balance of the sympathetic nervous system and parasympathetic nervous system. However, the specific relation between the autonomic nervous system response and the Cushing reflex and its symptoms has yet to be identified.It has been determined that rate of respiration is affected by the Cushing reflex, though the respiratory changes induced are still an area that needs more research.
Finally, the Cushing reflex may be one of many ways to identify if a patient has rejected a transplanted organ. Aside from the innate autoimmune response, ischemia in the cranial region has been detected with a transplanted organ that is being rejected. As such, the presence of a Cushing reflex due to ICP can indicate that ischemia may be occurring due to foreign organ rejection.As first postulated by Harvey Cushing, raised intracranial pressure is the primary cause of the Cushing reflex. Furthermore, continued moderate increases in cranial pressure allows for the Cushing reflex to occur. In contrast, rapid and dramatic pressure rises do not allow for the mechanism of the reflex to sufficiently take place. Elevated intracranial pressure can result from numerous pathways of brain impairment, including: subarachnoid hemorrhages, ischemia, meningitis, trauma, including concussions, hypoxia, tumors, and stroke. In one study, it was confirmed that raised ICP due to subarachnoid hemorrhaging causes mechanical distortion of the brainstem, specifically the medulla. Due to the mechanism of the Cushing reflex, brainstem distortion is then swiftly followed by sympathetic nervous system over activity. In addition, during typical neurosurgical procedures on patients, especially those involving neuroendoscopic techniques, frequent washing of the ventricles have been known to cause high intracranial pressure. The Cushing reflex can also result from low CPP, specifically below 15 mmHg. CPP normally falls between 70-90 mmHg in an adult human, and 60-90 mmHg in children.Brain plateau wave changes are also associated with the Cushing reflex.