A New Breakthrough in the Understanding of the Pathobiology of Stroke
The INR has made a stunning discovery: that the neurological status of patients following stroke, even years after the acute event, may rapidly improve following the use of an anti-TNF therapeutic.
These published results, and the subsequent clinical experience of INR physicians, suggest that excess TNF plays an important role in post-stroke chronic disability and establish the promise that the INR’s patented anti-TNF treatment presents for stroke recovery and stroke rehabilitation. Results can vary, and more than one dose may be necessary for optimal benefit, but these results represent a new breakthrough in the understanding of the neurological basis of chronic brain dysfunction following stroke.
Consultation for Stroke at the INR
Patients who have experienced stroke often have weakness or decreased sensation in one half of the body, cognitive or speech difficulties, or other neurological problems that can last for years. Consultation with an INR physician following hospital discharge is encouraged, even if the stroke has occurred years before. Please call the INR ((310) 479-0107(California) or, in Florida (561) 353-9707 for further information.
What is Stroke?
A stroke occurs when the blood supply to part of the brain is suddenly interrupted or when a blood vessel in the brain bursts, spilling blood into the spaces surrounding brain cells. Brain cells die when they no longer receive oxygen and nutrients from the blood or there is sudden bleeding into or around the brain. The symptoms of a stroke include sudden numbness or weakness, especially on one side of the body; sudden confusion or trouble speaking or understanding speech; sudden trouble seeing in one or both eyes; sudden trouble with walking, dizziness, or loss of balance or coordination; or sudden severe headache with no known cause. There are two forms of stroke: ischemic – blockage of a blood vessel supplying the brain, and hemorrhagic – bleeding into or around the brain, including ICH (intra-cerebral hemorrhage and SAH (subarachnoid hemorrhage).
Chronic neurological consequences of stroke
Although stroke is a disease of the brain, it can affect the entire body. A common disability that results from stroke is complete paralysis on one side of the body, called hemiplegia. A related disability that is not as debilitating as paralysis is one-sided weakness or hemiparesis. Stroke may cause problems with thinking, awareness, attention, learning, judgment, and memory. Stroke survivors often have problems understanding or forming speech. A stroke can lead to emotional problems. Stroke patients may have difficulty controlling their emotions or may express inappropriate emotions. Many stroke patients experience depression. Stroke survivors may also have numbness or strange sensations. The pain is often worse in the hands and feet and is made worse by movement and temperature changes, especially cold temperatures.
Recurrent stroke is frequent; about 25 percent of people who recover from their first stroke will have another stroke within 5 years.
Relevant 2012-2013 Scientific Publications
**Indicates articles of particular interest
1. Hughes, J.L., et al., A microPET study of the regional distribution of [11C]-PK11195 binding following temporary focal cerebral ischemia in the rat. Correlation with post mortem mapping of microglia activation. Neuroimage, 2012. 59(3): p. 2007-16.
2. Iliff, J.J., et al., A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid beta. Sci Transl Med, 2012. 4(147): p. 147ra111.
3. Roh, M., et al., Etanercept, a widely used inhibitor of tumor necrosis factor-alpha (TNF-alpha), prevents retinal ganglion cell loss in a rat model of glaucoma. PLoS One, 2012. 7(7): p. e40065.
**4. Santello, M. and A. Volterra, TNFalpha in synaptic function: switching gears. Trends Neurosci, 2012. 35(10): p. 638-47.
5. Smith, C., et al., The neuroinflammatory response in humans after traumatic brain injury. Neuropathol Appl Neurobiol, 2012.
**6. Tobinick, E., Deciphering the physiology underlying the rapid clinical effects of perispinal etanercept in Alzheimer’s disease. Curr Alzheimer Res, 2012. 9(1): p. 99-109.
**7. Tobinick, E., et al., Selective TNF Inhibition for Chronic Stroke and Traumatic Brain Injury : An Observational Study Involving 629 Consecutive Patients Treated with Perispinal Etanercept. CNS Drugs, 2012. 26(12): p. 1051-70.
**8. Blaylock, R.L., Immunology primer for neurosurgeons and neurologists part 2: Innate brain immunity. Surg Neurol Int, 2013. 4: p. 118.
**9. Cheong, C.U., et al., Etanercept attenuates traumatic brain injury in rats by reducing brain TNF- alpha contents and by stimulating newly formed neurogenesis. Mediators Inflamm, 2013. 2013: p. 620837.
**10. Chio, C.C., et al., Etanercept attenuates traumatic brain injury in rats by reducing early microglial expression of tumor necrosis factor-alpha. BMC Neurosci, 2013. 14(1): p. 33.
11. Efrati, S., et al., Hyperbaric oxygen induces late neuroplasticity in post stroke patients–randomized, prospective trial. PLoS One, 2013. 8(1): p. e53716.
12. Iwatsuki, K., et al., Targeting anti-inflammatory treatment can ameliorate injury-induced neuropathic pain. PLoS One, 2013. 8(2): p. e57721.
**13. Johnson, V.E., et al., Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain, 2013. 136(Pt 1): p. 28-42.
**14. King, M.D., C.H. Alleyne, Jr., and K.M. Dhandapani, TNF-alpha receptor antagonist, R-7050, improves neurological outcomes following intracerebral hemorrhage in mice. Neurosci Lett, 2013. 542: p. 92-6.
15. Kumar, A., et al., Traumatic brain injury in aged animals increases lesion size and chronically alters microglial/macrophage classical and alternative activation states. Neurobiol Aging, 2013. 34(5): p. 1397-411.
**16. Lei, B., et al., Tumor necrosis factor alpha antagonism improves neurological recovery in murine intracerebral hemorrhage. J Neuroinflammation, 2013. 10(1): p. 103.
17. Petzold, A. and A. Girbes, Pain management in neurocritical care. Neurocrit Care, 2013. 19(2): p. 232-56.
18. Starke, R.M., et al., Tumor Necrosis Factor-alpha Modulates Cerebral Aneurysm Formation and Rupture. Translational Stroke Research, 2013. 10.1007/s12975-013-0287-9.
**19. Waters, R.J., et al., Cytokine gene polymorphisms and outcome after traumatic brain injury. J Neurotrauma, 2013. 30(20): p. 1710-6.
**20. Works, M.G., J.B. Koenig, and R.M. Sapolsky, Soluble TNF receptor 1-secreting ex vivo-derived dendritic cells reduce injury after stroke. J Cereb Blood Flow Metab, 2013.
2013 Scientific Citations to publications of Edward Tobinick, M.D.
The following are selected publications that have cited scientific publications of Edward Tobinick M.D. in 2013:
1. Bai, L., et al., Elevated Plasma Levels of Soluble TNFRs and TACE Activity in Alzheimer’s Disease Patients of Northern Han Chinese Descent. Curr Alzheimer Res, 2013. 10(1): p. 57-62.
2. Blaylock, R.L., Immunology primer for neurosurgeons and neurologists part 2: Innate brain immunity. Surg Neurol Int, 2013. 4: p. 118.
3. Bohren, Y., et al., Antidepressants suppress neuropathic pain by a peripheral beta2-adrenoceptor mediated anti-TNFalpha mechanism. Neurobiol Dis, 2013. 60C: p. 39-50.
4. Borrelli, S., et al., Long-lasting efficacy of the cognitive enhancer cytotoxic necrotizing factor 1. Neuropharmacology, 2013. 64: p. 74-80.
5. Brambilla, L., F. Martorana, and D. Rossi, Astrocyte signaling and neurodegeneration: New insights into CNS disorders. Prion, 2013. 7(1): p. 28-36.
6. Camara, M.L., et al., TNF-alpha and its receptors modulate complex behaviours and neurotrophins in transgenic mice. Psychoneuroendocrinology, 2013.
7. Chengke, L., et al., Effect of infliximab combined with methylprednisolone on expressions of NF-kappaB, TRADD, and FADD in rat acute spinal cord injury. Spine (Phila Pa 1976), 2013. 38(14): p. E861-9.
8. Cheong, C.U., et al., Etanercept attenuates traumatic brain injury in rats by reducing brain TNF- alpha contents and by stimulating newly formed neurogenesis. Mediators Inflamm, 2013. 2013: p. 620837.
9. Clark, I.A. and B. Vissel, Treatment implications of the altered cytokine-insulin axis in neurodegenerative disease. Biochem Pharmacol, 2013. 86(7): p. 862-71.
10. Crow, M., F. Denk, and S.B. McMahon, Genes and epigenetic processes as prospective pain targets. Genome Med, 2013. 5(2): p. 12.
11. Cunningham, E.L. and A.P. Passmore, Drug development in dementia. Maturitas, 2013.
12. Deumens, R., et al., Prevention of chronic postoperative pain: cellular, molecular, and clinical insights for mechanism-based treatment approaches. Prog Neurobiol, 2013. 104: p. 1-37.
13. Elcioglu, H., et al., Thalidomide attenuates learning and memory deficits induced by intracerebroventricular administration of streptozotocin in rats. Biotech Histochem, 2013. 88(3-4): p. 145-52.
14. Enciu, A.M., M. Gherghiceanu, and B.O. Popescu, Triggers and effectors of oxidative stress at blood-brain barrier level: relevance for brain ageing and neurodegeneration. Oxid Med Cell Longev, 2013. 2013: p. 297512.
15. Gajewski, P.D., et al., The functional tumor necrosis factor-alpha (308A/G) polymorphism modulates attentional selection in elderly individuals. Neurobiol Aging, 2013.
16. Kaufman, E.L. and A. Carl, Biochemistry of Back Pain. The Open Spine Journal, 2013. 5: p. 12-18.
17. Kheirandish-Gozal, L. and D. Gozal, Genotype-phenotype interactions in pediatric obstructive sleep apnea. Respir Physiol Neurobiol, 2013.
18. Liu, Q., et al., Novel treatment of neuroinflammation against low back pain by soluble fullerol nanoparticles. Spine (Phila Pa 1976), 2013. 38(17): p. 1443-51.
19. Mika, J., W. Makuch, and B. Przewlocka, Preclinical Cancer Pain Models, in Cancer Pain, M. Hanna and Z. Zylicz, Editors. 2013, Springer London: London. p. 71-93.
20. Novac, N., Challenges and opportunities of drug repositioning. Trends Pharmacol Sci, 2013. 34(5): p. 267-72.
21. Petzold, A. and A. Girbes, Pain Management in Neurocritical Care. Neurocrit Care, 2013.
22. Puri, A.S., et al., Analysis of venous drainage in three patients with extradural spinal arteriovenous fistulae at the craniovertebral junction with potentially benign implication. J Neurointerv Surg, 2013.
23. Starke, R.M., et al., Tumor Necrosis Factor-alpha Modulates Cerebral Aneurysm Formation and Rupture. Translational Stroke Research, 2013. 10.1007/s12975-013-0287-9.
24. Strong, C., et al., Surgical treatment options and management strategies of metastatic renal cell carcinoma to the lumbar spinal nerve roots. J Clin Neurosci, 2013. 20(11): p. 1546-9.
25. Swardfager, W., et al., Interleukin-17 in post-stroke neurodegeneration. Neurosci Biobehav Rev, 2013. 37(3): p. 436-447.
26. Waters, R.J., et al., Cytokine gene polymorphisms and outcome after traumatic brain injury. J Neurotrauma, 2013. 30(20): p. 1710-6.
27. Yoshiyama, Y., V.M. Lee, and J.Q. Trojanowski, Therapeutic strategies for tau mediated neurodegeneration. J Neurol Neurosurg Psychiatry, 2013. 84(7): p. 784-95.
28. Zuliani, G., et al., Subsyndromal Delirium and Its Determinants in Elderly Patients Hospitalized for Acute Medical Illness. J Gerontol A Biol Sci Med Sci, 2013.