Electronic Supplementary Material
Accompanying the manuscript, “Immediate neurological recovery following perispinal etanercept
years after brain injury”
An objective review of the peer-reviewed medical literature establishes that the biological plausibility
of the rapid favorable neurological effects seen here and in others treated with perispinal etanercept is
unequivocal, and supported by extensive literature[1]:
1.
Published, peer-reviewed reports of improvement in cognition in humans following the use of
etanercept or TNF antibodies by independent academic sources other than the present authors[26];
2. Favorable results of etanercept and other recombinant TNF inhibitors in animal models of stroke,
traumatic brain injury, Alzheimer’s disease, and neuropathic pain[5-31];
3. Published, peer-reviewed reports of rapid, significant and sustained neurological and clinical
improvement following perispinal etanercept in patients with chronic neurological dysfunction
following stroke, traumatic brain injury, Alzheimer’s disease, sciatica and other forms of spinal
pain[1, 32-45];
4. Positron emission tomographic imaging data and data from direct pathological examination of
brain tissue demonstrating chronic microglial activation in the brain following stroke and
traumatic brain injury in humans that may last for years after a single brain injury[46-51];
5. Etanercept’s demonstrated ability to reduce microglial activation in multiple experimental models,
including in models of brain injury[18, 19, 22, 25, 52];
6. Known effects of TNF on synaptic function[2, 37, 53-61];
7. Known rapid effects of TNF on neuronal and synaptic function[59-64];
8. Recognition in the scientific community of the therapeutic potential of perispinal etanercept for
treatment of neurological disorders, as indicated by scientific citation[2, 3, 5, 6, 16, 17, 19, 20, 24,
28, 56, 65-103];
9. Four randomized, clinical trials reporting favorable effects of etanercept for spinal neuropathic
pain supporting earlier reports of the effectiveness of perispinal etanercept for these
indications[34, 35, 104-107];
10. A known anatomic pathway for carriage of etanercept following perispinal injection, the vertebral
venous plexus(Figure 1)[1, 42, 108-112].
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