Perispinal Delivery of CNS Drugs


Perispinal.DeliveryMay 2, 2016 (Los Angeles, Boca Raton): On April 27, 2016, the peer-reviewed review article entitled, Perispinal Delivery of CNS Drugs, by Edward Tobinick MD, published online in the scientific journal CNS Drugs. The abstract of the article states:

Perispinal injection is a novel emerging method of drug delivery to the central nervous system (CNS). Physiological barriers prevent macromolecules from efficiently penetrating into the CNS after systemic administration. Perispinal injection is designed to use the cerebrospinal venous system (CSVS) to enhance delivery of drugs to the CNS. It delivers a substance into the anatomic area posterior to the ligamentum flavum, an anatomic region drained by the external vertebral venous plexus (EVVP), a division of the CSVS. Blood within the EVVP communicates with the deeper venous plexuses of the CSVS. The anatomical basis for this method originates in the detailed studies of the CSVS published in 1819 by the French anatomist Gilbert Breschet. By the turn of the century, Breschet’s findings were nearly forgotten, until rediscovered by American anatomist Oscar Batson in 1940. Batson confirmed the unique, linear, bidirectional and retrograde flow of blood between the spinal and cerebral divisions of the CSVS, made possible by the absence of venous valves. Recently, additional supporting evidence was discovered in the publications of American neurologist Corning. Analysis suggests that Corning’s famous first use of cocaine for spinal anesthesia in 1885 was in fact based on Breschet’s anatomical findings, and accomplished by perispinal injection. The therapeutic potential of perispinal injection for CNS disorders is highlighted by the rapid neurological improvement in patients with otherwise intractable neuroinflammatory disorders that may ensue following perispinal etanercept administration. Perispinal delivery merits intense investigation as a new method of enhanced delivery of macromolecules to the CNS and related structures.

The full-text of the article is available by clicking on the link below:

Perispinal Delivery of CNS Drugs. Edward Tobinick MD. CNS Drugs. 2016:1-12. do:10.1007/s40263-016-0339-2, published online 27 April 2016. (Download free full-text PDF)

Jan Sanders returns to Boca Raton from Kennett, Missouri on March 11, 2013


We were so pleased that Jan returned to visit us on March 11 from Kennett, Missouri with her husband. She is holding the story the Daily Dunklin Democrat had printed on February 17 about her rapid clinical improvement after treatment.  To read the whole story please visit the story on the webpage of the Daily Dunklin Democrat (click here).jan.INR.boca.mar2013.7in.96dpi

Jan Sanders and Mary Jean Moore discuss their treatment results in the Daily Dunklin Democrat


Dear Friends,
The Daily Dunklin Democrat in Kennett, Missouri has today (February 17, 2013) published a wonderful new story about the results of treatment at the INR PLLC in Boca Raton following stroke.  To read the whole story please visit the story on the webpage of the Daily Dunklin Democrat (click here).

Please also see:
February 4, 2012 article in The Recorder, Greenfield, Massachusetts:

February 4, 2013 article in Massachusetts newspaper discusses new stroke treatment


February 4, 2012 article in The Recorder, Greenfield, Massachusetts:

New treatment gives stroke victim hope

Recorder/Paul Franz<br /><br /><br /><br /><br /><br />
Rodney Krug, 91, of Bernardston at the Bernardston Senior Center.Recorder/Paul Franz Rodney Krug, 91, of Bernardston at the Bernardston Senior Center.

Sunday, February 3, 2013
(Published in print: Monday, February 4, 2013)


For the full article, please go to:

Lead story on 60 Minutes Australia on November 6, 2011 features the INR


Pleased to announce that the lead story on 60 Minutes Australia on their November 6, 2011 broadcast is their in-depth report about Dr. Tobinick and the INR.

The transcript and full-story can be viewed here:

Many thanks to all our patients, friends, and staff that have helped to make this happen and bring this forward.

Validity of INR’s pioneering work re-confirmed


November 3, 2011

A newly published randomized study from Chiba University in Japan provides robust scientific support for the   pioneering work of the Institute of Neurological Recovery utilizing novel methods of delivery and indications for etanercept. The new study, published ahead-of-print in the leading journal Spine demonstrated the superiority of epidural administration of etanercept over an epidural steroid injection for treatment of sciatica associated with spinal stenosis. This method of treatment was invented at the INR (U.S. patent 6,419,944, issued to Edward Tobinick M.D., filed April 5, 2001). When the INR first published our work with etanercept for sciatica in 2003 and 2004 there were many who were [incorrectly] skeptical. This new study joins a favorable randomized, placebo-controlled study conducted by the U.S. Army in conjunction with Johns Hopkins researchers published in 2009 after their [uncredited] consultation with us several years before. Pleased that the truth has again been confirmed.

Anti-TNF Therapies for Rheumatoid Arthritis Could Reduce Alzheimer’s Risk


In the News: November 7, 2010

Anti-TNF Therapies for Rheumatoid Arthritis Could Reduce Alzheimer’s Risk

Source: American College of Rheumatology (ACR)

Newswise — Anti-TNF therapies commonly used to treat rheumatoid arthritis have been found to potentially reduce the risk of developing Alzheimer’s dementia among people with rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and destruction of the joints. People with RA often experience limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

A complication of chronic inflammation in RA is amyloidosis, caused by excess deposits of amyloid proteins in different organs, which can cause harmful effects to the normal function of many organs. While people with Alzheimer’s disease are found to have local deposits of a type of amyloid protein—beta-amyloid peptide—in the brain, the actual cause of Alzheimer’s remains unclear.

Researchers recently set out to evaluate if there is a relationship between different treatments for RA and the incidence of Alzheimer’s dementia. They reviewed medical and pharmacy claims data of over eight million subjects in the U.S. from a commercial database (Verisk Health). A total of 42,193 people with RA were identified. Each RA subject with newly diagnosed Alzheimer’s dementia was compared to 10 people with RA who did not have Alzheimer’s dementia (called “controls”). As researchers made these comparisons, they ensured they were comparing people of the same age, gender, and with the same use of methotrexate, a medication commonly used for RA. Researchers examined the exposure of these individuals to several drugs used to treat RA including sulfasalazine, prednisone, three anti-TNFs (infliximab, etanercept, and adalimumab) and rituximab.

A total of 165 RA subjects with Alzheimer’s dementia were compared to 1,383 RA controls without Alzheimer’s dementia. Researchers found that those who received anti-TNF treatment had a 55 percent reduction in risk of developing Alzheimer’s dementia. This effect was not seen with other drugs used for treatment of RA, including sulfasalazine, prednisone and rituximab


The researchers concluded that anti-TNF agents used to treat people with RA may be useful in reducing the development of Alzheimer’s dementia, although the mechanisms need further investigation.

“In this study, the incidence of Alzheimer’s disease was found to be lower in patients with rheumatoid arthritis who had been treated with anti-TNF agents,” says Dr. Richard Chou, MD, PhD; assistant professor at Dartmouth Medical School and lead investigator in the study. “Although the cause of Alzheimer’s disease is not known, the results suggest that TNF may play a role in its development.”

TNF-antagonists (also called biologics or anti-TNF therapy) are a class of drugs that have been used since 1998. Overall, they have been given to more than 600,000 people worldwide. These drugs are given to lessen inflammation by interfering with a biologic substance called TNF that cause or worsen inflammation.

Patients should talk to their rheumatologists to determine their best course of treatment.

The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit or join the conversation on Twitter by using the official hashtag: #ACR2010.


Editor’s Notes: Richard C. Chou, MD, PhD will present this research during the ACR Annual Scientific Meeting at the Georgia World Congress Center at 2:30 PM on Monday, November 8 in Room A411. Dr. Chou will be available for media questions and briefing at 1:30 PM on Tuesday, November 9 in the on-site press conference room, B 212.

Presentation Number: 640

Tumor Necrosis Factor Inhibition Reduces the Incidence of Alzheimer’s Disease in Rheumatoid Arthritis Patients

Richard C Chou, MD, PhD (Section of Rheumatology, Dartmouth-Hitchcock Medical Center and Dartmouth Medical School, Lebanon, NH)

Michael A Kane, MD (Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Massachusetts Institute of Technology, Boston, MA)

Sanjay Ghimire, MD (Verisk Health, Waltham, MA)

Shiva Gautam, PhD (Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA)

Body: Objective: To investigate the relationship between different rheumatoid arthritis treatments and Alzheimer’s dementia

Background: A complication of chronic inflammation in rheumatoid arthritis (RA) is the deposition of amyloid proteins, resulting in secondary amyloidosis. Alzheimer’s dementia (AD) is associated with the local deposition of beta-amyloid peptide in the brain, although the pathogenetic mechanisms of AD are unclear. The relationship between RA and AD has not been established.

Design/Methods: We reviewed medical and pharmacy claims data from January 2000 to November 2007 for a commercially insured cohort of 8.5 million adults throughout the US. We derived a subcohort of 42,193 patients with a pre-existing diagnosis of RA. In this subcohort, we conducted a nested case-control study of the incidence of AD. We excluded individuals with psoriatic arthritis, inflammatory bowel disease, previous stroke or previous AD. For each individual with newly diagnosed AD (cases) we matched up to 10 controls who did not have a prior diagnosis of AD and were free of AD during the exposure assessment period. Matching criteria included age, gender, duration of exposure assessment period and methotrexate treatment. We examined exposure to sulfasalazine, prednisone, three anti-tumor necrosis factor (TNF) agents (infliximab, etanercept, adalimumab) and rituximab.

Results: In this nested case-control study, a total of 165 patients with AD (cases) were matched to 1,383 controls without AD. Treatment with anti-TNF agents in RA was associated with lower risk for incident AD [adjusted odds ratio (OR) 0.440; 95% confidence interval (CI) 0.223-0.868; p=0. 0178). The risk of AD was not affected by exposure to sulfasalazine, prednisone or rituximab. The results were similar [adjusted OR 0.448; 95% CI 0.225-0.892; p = 0.0222) after adjustment for covariates, including hypertension, hyperlipidemia, diabetes mellitus, peripheral vascular disease, and coronary artery disease.

Conclusion: In this population of adults with RA, we observed that the risk of AD was reduced by TNF inhibitor therapy, but not by other disease modifying agents used for treatment of RA. Tumor necrosis factor may be an important component in the pathogenesis of AD.

Disclosure: Richard Chou, nothing to disclose; Michael Kane, Verisk Health: Consulting fees; Shiva Gautama, nothing to disclose, Sanjay Ghirmire, Verisk Health: Employment (full or part-time).

Welcome to the INR Blog


Welcome to the INR Blog!

This Blog is still in development. The aim of this blog is to add further scientific information to the content of the INR website as soon as it becomes available. If possible in the future postings and comments from website visitors will be enabled. Thank you for your interest.

Edward Tobinick MD

Recent published research results:

Anti-TNF-alpha reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains. Shi JQ, Shen W, Chen J, Wang BR, Zhong LL, Zhu YW, Zhu HQ, Zhang QQ, Zhang YD, Xu J. Brain Res. 2010 Oct 21.
Inflammation plays an important role in the pathogenesis of Alzheimer’s disease (AD). Overexpression of tumor necrosis factor-alpha (TNF-alpha) occurs in the AD brain. Recent clinical studies have shown that the anti-TNF-alpha therapy improves cognition function of AD patients rapidly. However, the underlying mechanism remains elusive. The present study investigates the effects of intracerebroventricular injection of the monoclonal TNF-alpha antibody, Infliximab, on the pathological features of AD in the APP/PS1 double transgenic mice. We found that Infliximab administration reduced the levels of TNF-alpha, amyloid plaques and tau phosphorylation as early as three days after daily injection of 150micrograms of Infliximab for three days. The number of CD11c-positive dendritic-like cells and the expression of CD11c were found to be increased concurrently after Infliximab injection. These data suggested that the CD11c-positive dendritic-like cells might contribute to the Infliximab-induced reduction of AD-like pathology. Further, our results support the use of anti-TNF-alpha for the treatment of AD. Read more

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