Has Neurotrauma Been Built on a Faulty Foundation?

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At a national neurosurgery meeting a few years back Sal Khan spoke about the Khan Academy, which he founded.  He emphasized the importance of one’s learning being built successively upon solid foundations of basic and then more advanced principles in order to achieve ultimate success.  Since listening to his interesting and inspiring words I have been perturbed by the possibility that neurotrauma’s failure to advance may relate to such a faulty foundation.  Could it be that we’ve got some basic tenets wrong and that we can’t move forward until we finally get it right?

Neurotrauma research has a short history and as a result the relatively small field can be deconstructed with relative ease – CT scanning and the introduction of the Glasgow Coma Scale in the 1970’s1 mark the advent of relevant research studies.  Around the same time basic scientists began investigations into cellular and molecular aspects of neurotrauma which had not previously been considered respectable work.  To date, however, no such effort has led to the translation of any safe and effective therapies for either traumatic brain or spinal cord injury.  Many have opined on the reasons for this failure.  I would like to add a few additional potential oversights to the list in hopes it helps the field to ultimately move forward.

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Papilledema: It has long been held that patients with brain injuries do not get papilledema.  This was most clearly articulated by Becker in his 1985 publication2.  Of course head injured patients DO get papilledema, and there has been renewed interest in the optic nerve sheath diameter as an apparently accurate surrogate measure of intracranial pressure.

The Kellie-Monro Doctrine: Modern efforts to paraphrase the 200 year old works of Kellie3 and Monro4 are quite different than what was actually written by these Scottish luminaries.  The modern interpretation of this doctrine is taught in medical school – and in ATLS – as one of the most basic principles of TBI physiology.  While the notion of displacement of venous blood during intracranial pressure elevation is undoubtedly true, the Kellie-Monro doctrine is at odds with the vasodilatory and vasoconstriction cascades described by Rosner5.  Indeed, it is our belief that Lundberg’s work in the 1960’s demonstrating an increase in cerebral blood volume during plateau waves (apparently causing the plateau waves)6 is a clear disproval of key tenets of the Kellie-Monro doctrine.  Our view is that modern TBI curricula would serve patient care better if they taught Rosner’s vasodilation and vasoconstriction cascades as they comprise a more comprehensive, accurate and relevant model for intracranial pressure changes.

Cortical Spreading Depressions and Depolarizations (CSDs):  Despite their discovery in 1944 in the brains of rabbits by the Brazilian Leao7, we’ve overlooked (and filtered out) these phenomena in human patients.  CSDs are increasingly well understood and they have the ability to explain a number of phenomena previously difficult to understand such as non-epileptiform, transient focal neurological deficits and cerebral infarctions.  CSDs have been an inconvenient truth for the majority of us who lack the skillset to monitor them, but now that it has been repeatedly demonstrated that they can be treated with ketamine8 our field needs to rapidly investigate and learn about these phenomena and determine if they should be routinely monitored and treated.

Autoregulation:  The SIBICC algorithms9,10 broke ground in asserting that the principles of cerebral autoregulation are fundamental to modern TBI management.   Moreover the SIBICC effort asserts that all practitioners caring for TBI patients should understand how to determine a patient’s autoregulatory status and how to incorporate this status into the management plan.  It is remarkable that until recently most brain injury care has been ignorant of autoregulatory status.

CNS-Directed Autoimmunity After CNS Injury: Delayed dementia after TBI and SCI could be a consequence of the persistent neuroinflammation seen in the brain following both conditions.  The Hawryluk laboratory has published evidence suggesting that this persistent neuroinflammation could result from CNS-directed autoimmunity, as indeed the CNS is normally immuniprivileged11.  Despite the phenomenon of sympathetic opthalmia and the acceptance of autoimmunity following ischemic stroke, neurosurgeons have been slow to consider that CNS-directed autoimmunity following CNS injury may have deleterious effects.

The Big Picture: Perhaps we have had too few thought leaders in neurotrauma.  Perhaps we have not had enough bright minds in the field questioning each other.  Perhaps too few lessons are being passed to too small a group of new neurotraumatologists.  Without a doubt it is incumbent upon all neurosurgeons, and especially junior ones interested in neurotrauma to question everything.  All of the fundamentals  should be questioned – nothing is sacred.  A lack of theories and hypotheses is arguably a greater problem than research funding at this time.

Moving Forward – Lumbar CSF Drainage to Abort Intracranial Hypertension: We are working to advance a novel therapeutic approach for intracranial pressure treatment which challenges traditional thinking.  Recent evidence has suggested that cerebrospinal fluid in the brain’s basal cisterns is not effectively drained by a ventriculostomy12.  It is acknowledged that lumbar cerebrospinal fluid drainage has typically been viewed as contraindicated in brain injured patients.  Nonetheless, we believe it may be possible – in carefully selected patients – to safely drain CSF and to prevent or attenuate problematic intracranial pressure elevation.  This idea must be subject to rigorous study with careful attention to safety, but this dogma-questioning approach may ultimately exemplify the type of thinking the field needs to advance.

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