Perispinal administration of etanercept helps to improve neurological dysfunction following stroke or traumatic brain injury


An observational study has provided clinical evidence that chronic neurological dysfunction from stroke or traumatic brain injury can rapidly improve following perispinal administration of etanercept, a drug that targets brain inflammation, even years or decades after the initial event. The study titled “Selective TNF (tumour necrosis factor) inhibition for chronic stroke and traumatic brain injury” has been published online ahead-of-print in the journal CNS Drugs and will be published in the 1 December print issue. 

According to background information provided by study author Edward Tobinick, Institute of Neurological Recovery, Los Angeles, USA, and colleagues: “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).”

The authors also suggested that from previous experimental data, etanercept, a selective TNF inhibitor, may improve microglial activation and modulate the adverse synaptic effects of excess TNF. Therefore, the researchers set out to evaluate the clinical response following perispinal administration of etanercept—a novel drug delivery method patented by Tobinick—in a cohort of patients with chronic neurological dysfunction after stroke and TBI. Tobinick et al wrote that “there is currently no drug treatment that is specifically approved to treat the spectrum of chronic neurological dysfunction affecting the 4.5 million survivors of stroke in the USA.”

Tobinick et al highlighted that previous clinical evidence has suggested “the potential of perispinal administration of etanercept for rapid relief of pain and neurological dysfunction due to herniated nucleus pulposus and spinal pain due to bone metastases.” Treatment of Alzheimer’s disease and related forms of dementia with perispinal etanercept has also been studied with results of “rapid and sustained improvement in cognitive function,” the authors wrote.         

The study was conducted at the Institute of Neurological Recovery in California and Florida, USA, from 1 November 2010 to 14 July 2012 and included 629 patients treated open-label. The researchers reviewed 617 patients (mean age 65.8 years±13.15, range 13–97) treated an average of 42±57.84 months (range 0.5–419) after stroke, and 12 patients (mean age 34.7±13.8, range 19–52) treated an average of 115.2±160.22 months (range 4–537) after TBI.  


In the stroke group, the researchers found that there were statistically significant improvements immediately, one week and three weeks after treatment in motor impairment, spasticity, sensory impairment, cognition, psychological/behavioural function, aphasia and pain, and some other improvements such as reductions in pseudobulbar affect and urinary incontinence. In the TBI cohort, motor impairment and spasticity were statistically reduced. The authors also noted a strong positive effect of treatment in the subgroup of patients treated more than 10 years after stroke and TBI (see Table 1 and Table 2).

Table 1      
STROKE COHORT: Changes in impairment, by impairment type and time point, after a single dose of perispinal etanercept
  Immediately After 1 week After 3 weeks
Motor 93.40% 89.80% 89%
p value <0.0001 <0.0001 <0.0001
Spasticity 85.60% 82.90% 81%
p value <0.0001 <0.0001 <0.0001
Cognitive 75.10% 86.50% 85.80%
p value <0.0001 <0.0001 <0.0001
Aphasia 60.10% 76.40% 77.60%
p value 0.0008 <0.0001 <0.0001
Pain 50.20% 72.10% 73.10%
p value >0.999 <0.0001 <0.0001
Patients N=617 / Average years: 65.8 / Average months since stroke: 42  
Table 2      
TBI COHORT: Changes in impairment, by impairment type and time point, after a single dose of perispinal etanercept
  Immediately After 1 Week After 3 Weeks
Motor 90.90% 100% 100%
p value 0.0117 0.001 0.0078
Spasticity 100% 100% 100%
p value 0.0039 0.0039 0.0312
Patients N=12 / Average years 34.7 / Average months since TBI: 115.2


The authors concluded that “Perispinal administration of etanercept produces clinical improvement in patients with chronic neurological dysfunction following stroke and TBI.” They also recognised the significance that the therapeutic possibilities extend beyond a decade after stroke and TBI. They also acknowledged the need to undertake randomised clinical trials “to further quantify and characterise the clinical response.”

Tobinick explained to
NeuroNews how perispinal etanercept works and the reason why it is effective in the improvement of chronic neurological dysfunction, he commented: “The patented drug delivery method utilised in this study was perispinal extrathecal administration followed by Trendelenburg positioning, a brief, relatively non-invasive office procedure, not requiring anaesthesia, that delivers etanercept (or other large molecules) into the cerebrospinal venous system. This method bypasses the blood-cerebrospinal barrier, rapidly delivering etanercept into the cerebrospinal fluid and into the brain, resulting in rapid clinical improvement (beginning within minutes), due to neutralisation of excess TNF.”  

Tobinick also commented on the significance of this study in terms of therapeutic possibilities for stroke and TBI patients: “These results demonstrate that it is now possible to provide rapid clinical benefit to patients even years or decades after stroke or TBI, utilising this unique therapeutic approach. This is the first effective treatment for the spectrum of chronic neurological dysfunction caused by stroke and/or TBI. These results also demonstrate the central involvement, and potential reversibility of pathophysiology mediated by excess TNF in chronic neurological disability caused by stroke and TBI.”