Table 1.

Contemporary neuroscience challenges to clinical practice standards for brain death determination

Brain death determination*

Contemporary neuroscience challenges

Documentation on clinical examination  Unresponsiveness (unconsciousness)  Absent brainstem reflexes  Positive apnea test Reversible causes must be excluded Confirmatory tests are only required when  There is uncertainty about clinical examination  An apnea test cannot be performed Cessation of functions of the whole brain are not required Neuronal necrosis at autopsy is not required to confirm the irreversibility of ceased brain functions

Bedside behavioral assessment of unresponsiveness does not necessarily equate with absent capacity for consciousness Cranial nerve motor (brainstem) reflexes cannot discern retained higher brain (telencephalon and diencephalon) functions Spontaneous movements and motor responses are postulated to be spinal automatisms and reflexes, respectively, because of spinal cord disconnection from supraspinal control, which also refutes the hypothesis that supraspinal (brainstem) control of respiration is being tested during the apnea test Situations when cessation of brain functions may not be irreversible   There is the presence of normal brainstem and higher brain structures at autopsy   Reduction in global blood flow to the whole brain can suppress supraspinal synaptic transmission and brainstem reflexes without triggering irreversible neuronal damage and necrosis (global ischemic penumbra)   Living-like electrophysiologic responses of hippocampal body and parahippocampal gyrus of the fixed postmortem normal human brain are demonstrable in vitro  Neurogenesis and neuroplasticity of the adult brain can regenerate and reestablish neuronal connectivity after injury

*The American Academy of Neurology Practice Parameter 2010 Evidence-based guideline update is the contemporary US standard in brain death determination (Wijdicks et al. 2010). Optional confirmatory tests may include electroencephalography, radioactive isotope cerebral perfusion scan, or cerebral vessel angiography. Contemporary neuroscience challenges also apply to other clinical practice standards for brain death determination such as the UK code of practice (The Academy of Medical Royal Colleges, 2008), the Canadian forum recommendations (Shemie et al. 2006), and the World Health Organization international guidelines (Shemie et al. 2014)