Track topics on Twitter Track topics that are important to you
Brain injury from stroke and traumatic brain injury (TBI) may result in a persistent neuroinflammatory response in the injury penumbra. This response may include microglial activation and excess levels of tumour necrosis factor (TNF). Previous experimental data suggest that etanercept, a selective TNF inhibitor, has the ability to ameliorate microglial activation and modulate the adverse synaptic effects of excess TNF. Perispinal administration may enhance etanercept delivery across the blood-CSF barrier.
The objective of this study was to systematically examine the clinical response following perispinal administration of etanercept in a cohort of patients with chronic neurological dysfunction after stroke and TBI.
After approval by an independent external institutional review board (IRB), a chart review of all patients with chronic neurological dysfunction following stroke or TBI who were treated open-label with perispinal etanercept (PSE) from November 1, 2010 to July 14, 2012 at a group medical practice was performed.
The treated cohort included 629 consecutive patients. Charts of 617 patients following stroke and 12 patients following TBI were reviewed. The mean age of the stroke patients was 65.8 years ± 13.15 (range 13-97). The mean interval between treatment with PSE and stroke was 42.0 ± 57.84 months (range 0.5-419); for TBI the mean interval was 115.2 ± 160.22 months (range 4-537). Statistically significant improvements in motor impairment, spasticity, sensory impairment, cognition, psychological/behavioural function, aphasia and pain were noted in the stroke group, with a wide variety of additional clinical improvements noted in individuals, such as reductions in pseudobulbar affect and urinary incontinence. Improvements in multiple domains were typical. Significant improvement was noted irrespective of the length of time before treatment was initiated; there was evidence of a strong treatment effect even in the subgroup of patients treated more than 10 years after stroke and TBI. In the TBI cohort, motor impairment and spasticity were statistically significantly reduced.
Irrespective of the methodological limitations, the present results provide clinical evidence that stroke and TBI may lead to a persistent and ongoing neuroinflammatory response in the brain that is amenable to therapeutic intervention by selective inhibition of TNF, even years after the acute injury.
Excess TNF contributes to chronic neurological, neuropsychiatric and clinical impairment after stroke and TBI. Perispinal administration of etanercept produces clinical improvement in patients with chronic neurological dysfunction following stroke and TBI. The therapeutic window extends beyond a decade after stroke and TBI. Randomized clinical trials will be necessary to further quantify and characterize the clinical response.
Institute of Neurological Recovery, 100 UCLA Medical Plaza, Suites 205-210, Los Angeles, CA, 90095, USA, firstname.lastname@example.org.
This article was published in the following journal.
Name: CNS drugs
To determine the prevalence and potential risk factors of acute and chronic post-traumatic headache (PTH) in patients with mild to moderate traumatic brain injury (TBI) in a prospective longitudinal o...
Traumatic brain injury outcomes can be classified as acute or chronic. Acute outcomes refer to injuries that occur immediately at the time of the injury and subsequent short-term consequences. Chronic...
To prospectively examine the association between intracortical inhibition and functional recovery following mild traumatic brain injury (mTBI).
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. Chronic traumatic encephalopathy symptoms include changes in mood, behavior, cognition, and mo...
To examine the length of time to return to work (RTW) among service members and veterans (SM/V) with traumatic brain injury (TBI) and to identify variables predictive of RTW.
In the search for a novel marker of stroke that could be rapidly assessed in blood, the investigators developed a point-of-care (POC) lateral flow device (LFD) that rapidly (< 15 min) dete...
Traumatic brain injury is an extremely common disease, it counts 50.000 deaths and 235.000 hospitalizations every year. Functional consequences of an acquired brain injury have a considera...
The NCTT is a prospective, multicenter, observational research network for subjects with chronic spinal cord and/or chronic traumatic brain injury.
This is an observational research study whose purposes are to see: 1. if 40 Hyperbaric Oxygen Therapy sessions at 1.5 atmospheres (HBOT 1.5) or more (60, or 80 HBOT's) help, worsen...
The aim of the study is to evaluate the cortical excitability in the severe brain injured patients. We hypothesize that: 1. There is a continuous decrease in intracortical inhibition fr...
Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.
Prolonged unconsciousness from which the individual cannot be aroused, associated with traumatic injuries to the BRAIN. This may be defined as unconsciousness persisting for 6 hours or longer. Coma results from injury to both cerebral hemispheres or the RETICULAR FORMATION of the BRAIN STEM. Contributing mechanisms include DIFFUSE AXONAL INJURY and BRAIN EDEMA. (From J Neurotrauma 1997 Oct;14(10):699-713)
A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.
Traumatic injuries to the cranium where the integrity of the skull is not compromised and no bone fragments or other objects penetrate the skull and dura mater. This frequently results in mechanical injury being transmitted to intracranial structures which may produce traumatic brain injuries, hemorrhage, or cranial nerve injury. (From Rowland, Merritt's Textbook of Neurology, 9th ed, p417)
Conditions characterized by persistent brain damage or dysfunction as sequelae of cranial trauma. This disorder may result from DIFFUSE AXONAL INJURY; INTRACRANIAL HEMORRHAGES; BRAIN EDEMA; and other conditions. Clinical features may include DEMENTIA; focal neurologic deficits; PERSISTENT VEGETATIVE STATE; AKINETIC MUTISM; or COMA.
Cytokine Tumour Necrosis Factor (TNF)
TNF is a compound that is classified as a cytokine which plays a central role in the cellular mechanisms of apoptosis or cell death. However, there are a number of different kinds of TNF, just under twenty, but the family of molecules have very similar a...
Women's Health - key topics include breast cancer, pregnancy, menopause, stroke Follow and track Women's Health News on BioPortfolio: Women's Health News RSS Women'...
Anxiety is caused by stress. It is a natural reaction, and is beneficial in helping us deal with tense situations and pressure. It is deterimental when is becomes an excessive, irrational dread of everyday situations. The most common types of anxiety di...