Perispinal Etanercept – Chronic Brain Injury
A new case report by Tobinick et al. in the May 2014 issue of Clinical Drug Investigation describes striking success with a single perispinal etanercept dose in a patient who sustained brain injury 3 years prior.
Multiple reports have shown promise for use of etanercept, a tumor necrosis factor (TNF) inhibitor, in patients with chronic neurological deficits associated with stroke, traumatic brain injury, Alzheimer’s disease, and chronic pain. Perispinal administration accesses the vertebral venous plexus and carries the medication via the cerebrospinal venous system to the brain. The rationale for etanercept use is based on evidence that TNF is involved in microglial activation, synaptic dysfunction, and neuropathic pain, while imaging has shown that chronic neuroinflammation persists for years following brain injury.
The 52-year-old patient described in this report had persistent language impairment, hemiparesis, and hemisensory disturbances over 3 years following an episode of status epilepticus, despite intensive rehabilitation therapy. After perispinal etanercept injection, coauthors Drs. Robert N. Spengler and Tracey A. Ignatowski, who study inflammatory and neuromodulatory functions of TNF, noted improvements in gait and verbal fluency within minutes. Patient continued to show improvement in all areas of prior deficit over the next 6 days, which were sustained at last follow up 6 weeks later without further medication.
While more research is needed and etanercept carries the rare potential risks of death, infection, seizures, and further injury, the experience with this patient, as well as with over 600 patients with chronic post-stroke neurological dysfunction (Tobinick, E., N.M. Kim, 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), expands the range of neurologic injuries that can potentially be addressed with perispinal etanercept used off-label and provides hope that impaired patients can regain function years after conventional rehabilitation attempts have failed.
Source: Clin Drug Investig, 2014, 34:361-6. doi: 10.1007/s40261-014-0186-1.
Read more: Clinical Drug Investigation
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Cover Image Credit: PET images of a living rat brain following peripheral administration of 64Cu-DOTA-etanercept. The distinctive central pattern of brain distribution suggests penetration of 64Cu-DOTA-etanercept into the CSF in the lateral and third ventricles and accumulation of tracer within the choroid plexus following perispinal administration. (A) The pattern following perispinal administration is distinct from that following ventral tail vein injection. (B) Comparison of the transverse PET image following perispinal injection with section 306 from the Allen Brain atlas . CSF: Cerebrospinal fluid; DOTA: 1,4,7,10-tetraazadodecane-N,NI,NII,NIII-tetraacetic acid. From: Perispinal etanercept: A new therapeutic paradigm in neurology, by Edward Tobinick, June 2010 Expert Review of Neurotherapeutics 10(6):985-1002
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