Why Do You Prescribe Methylprednisolone for Acute Spinal Cord Injury? A Canadian Perspective and a Position Statement [Archive]

Max

08-21-2002, 01:25 PM

Why Do You Prescribe Methylprednisolone for Acute Spinal Cord Injury? A Canadian Perspective and a Position Statement

R.J. Hurlbert, R. Moulton

Abstract: Objective: To determine the practice patterns for methylprednisolone administration for patients with acute spinal cord injury (SCI) within the spinal surgery community across Canada, and the reasons behind these patterns. Methods: Canadian neurological and orthopedic spine surgeons were surveyed at their respective annual meetings with a questionnaire asking seven questions with respect to their practice standards. Results: Sixty surgeons completed the survey representing approximately two-thirds of surgeons treating acute SCI within Canada. The NASCIS III dosing regimen is the most commonly prescribed steroid protocol. However, one-quarter of surgeons do not administer steroids at all. Of those who administer methylprednisolone, most do so because of peer pressure or out of fear of litigation. Conclusions: The vast majority of spine surgeons in Canada either do not prescribe methylprednisolone for acute SCI, or do so for what might be considered the wrong reasons. These results demonstrate the need for an evidence-based practice guideline. The Candian Spine Society and the Canadian Neurosurgical Society fully endorse the recommendations of the steroid task force (see preceding paper).

RÃ©sumÃ©: Pourquoi prescrire de la mÃ©thylprednisolone dans les cas de lÃ©sion aiguÃ« de la moelle Ã©piniÃ¨re? Perspective canadienne et dÃ©claration de principe. Objectif: DÃ©terminer les modalitÃ©s d'administration de la mÃ©thylprednisolone chez les patients prÃ©sentant une lÃ©sion aiguÃ« de la moelle Ã©piniÃ¨re (LMÃ‰) en chirurgie de la moelle Ã©piniÃ¨re au Canada et les raisons sous-jacentes Ã* ces pratiques. MÃ©thodes: Nous avons fait un sondage auprÃ¨s des neurochirurgiens et des orthopÃ©distes lors de leur congrÃ¨s annuel respectif au moyen d'un questionnaire incluant sept questions sur leurs standards de pratique. RÃ©sultats: Soixante chirurgiens ont complÃ©tÃ© le sondage, soit environ les deux tiers des chirurgiens qui traitent des LMÃ‰ au Canada. Le rÃ©gime posologique NASCIS III est le protocole d'administration de stÃ©roÃ¯des le plus couramment prescrit. Cependant, le quart des chirurgiens ne prescrivent pas du tout de stÃ©roÃ¯des. Parmi ceux qui administrent de la mÃ©thylprednisolone, la plupart le font Ã* cause de la pression des pairs ou par crainte d'une poursuite. Conclusions: La grande majoritÃ© des chirurgiens qui traitent des traumatisÃ©s de la moelle au Canada ne prescrivent pas de mÃ©thylprednisolone pour une LMÃ‰ ou le font pour ce qui pourrait Ãªtre considÃ©rÃ© comme de mauvaises raisons. Ces rÃ©sultats dÃ©montrent qu'il existe un besoin quant Ã* l'Ã©tablissement de lignes directrices basÃ©es sur des donnÃ©es probantes. La Canadian Spine Society et la Canadian Neurosurgical Society appuient entiÃ¨rement les recommandations du groupe de travail sur les stÃ©roÃ¯des (voir l'article prÃ©cÃ©dent).

Can. J. Neurol. Sci. 2002; 29: 236-239

==============================
"With every scientific advance, we grow closer to unlocking the mysteries of life and creation. But what have we gained if in the process, we lose our humanity. The most powerful thing we pass along to our children may not reside in the genes, but in the soul."
The Outer Limits(Criminal Nature)

Max

08-21-2002, 01:28 PM

me & many after me did not get it!!!

What a criminal stupidity http://sci.rutgers.edu/forum/images/smilies/mad.gif http://sci.rutgers.edu/forum/images/smilies/mad.gif http://sci.rutgers.edu/forum/images/smilies/mad.gif http://sci.rutgers.edu/forum/images/smilies/mad.gif

==============================
"With every scientific advance, we grow closer to unlocking the mysteries of life and creation. But what have we gained if in the process, we lose our humanity. The most powerful thing we pass along to our children may not reside in the genes, but in the soul."
The Outer Limits(Criminal Nature)

Max

08-21-2002, 01:29 PM

High-Dose Methylprednisolone for Acute Closed Spinal Cord Injury - Only a Treatment Option
H. Hugenholtz, D.E. Cass, M.F. Dvorak, D.H. Fewer, R.J. Fox, D.M.S. Izukawa,
J. Lexchin, S. Tuli, N. Bharatwal, C. Short

Abstract: Background: A systematic review of the evidence pertaining to methylprednisolone infusion following acute spinal cord injury was conducted in order to address the persistent confusion about the utility of this treatment. Methods: A committee of neurosurgical and orthopedic spine specialists, emergency physicians and physiatrists engaged in active clinical practice conducted an electronic database search for articles about acute spinal cord injuries and steroids, from January 1, 1966 to April 2001, that was supplemented by a manual search of reference lists, requests for unpublished additional information, translations of foreign language references and study protocols from the author of a Cochrane systematic review and Pharmacia Inc. The evidence was graded and recommendations were developed by consensus. Results: One hundred and fifty-seven citations that specifically addressed spinal cord injuries and methylprednisolone were retrieved and 64 reviewed. Recommendations were based on one Cochrane systematic review, six Level I clinical studies and seven Level II clinical studies that addressed changes in neurological function and complications following methylprednisolone therapy. Conclusions: There is insufficient evidence to support the use of high-dose methylprednisolone within eight hours following an acute closed spinal cord injury as a treatment standard or as a guideline for treatment. Methylprednisolone, prescribed as a bolus intravenous infusion of 30 mg per kilogram of body weight over fifteen minutes within eight hours of closed spinal cord injury, followed 45 minutes later by an infusion of 5.4 mg per kilogram of bodyweight per hour for 23 hours, is only a treatment option for which there is weak clinical evidence (Level I- to II-1). There is insufficient evidence to support extending methylprednisolone infusion beyond 23 hours if chosen as a treatment option.

RÃ©sumÃ©: MÃ©thylprednisolone Ã* haute dose dans les traumatismes aigus fermÃ©s de la moelle Ã©piniÃ¨re -une option thÃ©rapeutique.
Introduction: Une revue systÃ©matique des donnÃ©es concernant l'infusion de mÃ©thylprednisolone suite Ã* un traumatisme aigu de la moelle Ã©piniÃ¨re a Ã©tÃ© effectuÃ©e afin de clarifier la confusion qui rÃ¨gne sur l'utilitÃ© de ce traitement MÃ©thodes: Un comitÃ© formÃ© de spÃ©cialistes en neurochirurgie et en chirurgie orthopÃ©dique de la colonne vertÃ©brale, d'urgentologues et de physiatres en pratique clinique active a procÃ©dÃ© Ã* une recherche Ã©lectronique de bases de donnÃ©es pour identifier des articles sur les traumatismes aigus de la moelle Ã©piniÃ¨re et l'administration de stÃ©roÃ¯des, du 1er janvier 1966 Ã* avril 2001. Une recherche manuelle de listes de rÃ©fÃ©rences, la quÃªte d'informations additionnelles non publiÃ©es, la traduction de rÃ©fÃ©rences en langues Ã©trangÃ¨res et le protocole d'Ã©tude de l'auteur d'une Cochrane systematic review et de Pharmacia inc. ont Ã©tÃ© utilisÃ©s comme sources d'informations d'appoint. Les donnÃ©es ont Ã©tÃ© pondÃ©rÃ©es et des recommandations ont Ã©tÃ© dÃ©veloppÃ©es par consensus. RÃ©sultats: Cent cinquante-sept citations qui traitaient spÃ©cifiquement de traumatisme de la moelle Ã©piniÃ¨re et de mÃ©thylprednisolone ont Ã©tÃ© identifiÃ©es et soixante-quatre ont Ã©tÃ© revues. Les recommandations ont Ã©tÃ© basÃ©es sur une revue systÃ©matique Cochrane, six Ã©tudes cliniques de niveau I et sept Ã©tudes de niveau II qui traitaient de modifications de la fonction neurologique et de complications suite au traitement par la mÃ©thylprednisolone. Conclusions: Il n'y a pas suffisamment de donnÃ©es pour appuyer l'utilisation de la mÃ©thylprednisolone Ã* haute dose en dedans de huit heures aprÃ¨s un traumatisme aigu fermÃ© de la moelle Ã©piniÃ¨re comme traitement standard ou comme ligne directrice de traitement. La mÃ©thylprednisolone prescrite en infusion intraveineuse en bolus de 30 mg par kilogramme de poids corporel sur une pÃ©riode de quinze minutes en dedans de huit heures d'un traumatisme fermÃ© de la moelle, suivie 45 minutes plus tard d'une infusion de 5,4 mg par kilogramme de poids Ã* l'heure pendant 23 heures est seulement une option thÃ©rapeutique en faveur de laquelle il n'y a que des donnÃ©es cliniques faibles (Niveau I Ã* II-1). Il n'y a pas suffisamment de donnÃ©es pour recommander de prolonger l'infusion de mÃ©thylprednisolone au delÃ* de vingt-trois heures si on choisit cette option thÃ©rapeutique.

Can. J. Neurol. Sci. 2002; 29: 227-235

==============================
"With every scientific advance, we grow closer to unlocking the mysteries of life and creation. But what have we gained if in the process, we lose our humanity. The most powerful thing we pass along to our children may not reside in the genes, but in the soul."
The Outer Limits(Criminal Nature)

Wise Young

08-22-2002, 10:53 AM

It is difficult to address the criticism in these articles because the authors are basing their criticism on a misunderstanding of the clinical trials that were carried out and some artificial standard of what consistutes sufficient evidence to justify use of a drug. Perhaps some of the people who wrote these articles would come to this site and help clarify.

Most of these articles claim that NASCIS 2 and 3 were based on post-hoc analyses of data. The term post-hoc is a Latin word that indicates that the analyses were concocted after the study was done. Post-hoc analyses are frowned upon in clinical trials because one can always make up some kind of analysis that shows positive results after the trial. But, NASCIS analysis was not post-hoc. It was our original hypothesis that timing of therapy made a difference and the trial was designed to test this. For this reason, the trial compared patients that were treated before and after the median time of treatment (median time means half of the patients were treated before and half were treated after the time). In NASCIS 2, the median time of treatment was 8 hours. As it turns out, only those patients that were treated within 8 hours showed a statistically significant effect of methylprednisolone. The main criticism is not that the data is not significant but that the analysis was post-hoc. In my opinion, this criticism is not valid because the hypothesis and the design of the trial before the trial started was that there would be a difference due to timing.

Some people thought that the trial was invalid because the analysis segregated complete and incomplete patients. This was also part of the trial design because we knew that the recovery patterns of these patients would be very different. Therefore, the trial was designed to stratify these patients into two groups. Incidentally, the analysis also separated patients into cervical and thoracic spinal cord injuries because we thought that these patients may have different recovery patterns. These were also part of the trial design and should not be considered post-hoc.

The critiques threw out the studies based on their erroneous assumption that the trial analysis was post-hoc. Because they threw out the data and of course the data that remains is not sufficient to prove that the methylprednisolone is effective, they are claiming that the treatment is not effective and therefore should not be used. This is circular reasoning. When clinicians or scientists disbelieve a particular study, it is their obligation to collect new data that shows that the previous data is wrong and propose a better alternative. Rather than fulfilling this obligation (because none of the critics have suggested a better treatment or carried out a trial that is valid), they have chosen to attack methylprednisolone rather than coming out with a better one.

Some of the critics have suggested that because methylprednisolone is now the standard therapy, this is discouraging further clinical trials since they must compare all new therapies against methylprednisolone. My answer to this is that they can't have their cake and eat it, too. If they believe the methylprednisolone is ineffective, then it is the perfect placebo against which to compare their new treatment. If their new treatment is not as effective as methylprednisolone, this means that methylprednisolone should be used. This is common sense.

If methylprednisolone poses a considerable risk to the patients, perhaps the criticism would be justified. However, to date, there has not been any convincing evidence that a 30 mg/kg bolus of methylprednisolone followed by 23 hours of 5.4 mg/kg/hour increases morbidity or mortality after spinal cord injury. Over the past 10 years, probably over a million people have received this treatment (methylprednisolone is not only use for spinal cord injury but for multiple sclerosis). If the drug has serious side-effects, it certainly would have been reported by now. By the way, there is some evidence (from NASCIS 3) to suggest that a 48-hour course of methylprednisolone does increase the severity of pneumonia. This was the main reason that the 48-hour course of the treatment should not be used unless patients were treated between 3 to 8 hours after injury. NASCIS 3 showed that the 48-hour course of the drug is significantly superior to the 24-hour course of the drug when the drug is started more than 3 hours after injury.

Finally, I question the motivation of clinicians who are spending so much of their time attacking a 10-year old drug. Why are they doing this? There is currently no alternative to methylprednisolone for acute spinal cord injury. There has been unanimous agreement amongst all the clinicians and scientists in the field that we need a therapy that is better than methylprednisolone. Instead of spending all their time attacking an old therapy, they should be developing and testing a better treatment approach. All this squabbling should stop.

Wise.

[This message was edited by Wise Young on Aug 22, 2002 at 02:09 PM.]

kate

08-22-2002, 09:10 PM

Dr. Young, it makes me dizzy to think that if we lived 200 miles north, in British Columbia, my husband would not have been given MP a year and a half ago. Thank you for putting up with all of it, and for keeping on keeping on! You made our lives possible.

Kate

Karen'sMom

08-23-2002, 12:07 AM

It enrages me that my daughter was not given Methylprednisolone within 8 hours of her injury. It was not until after she was transferred to a bigger/better Hospital that she was given it for 24 hours. What can be done about informing these Emergency Doctors how important it is??? This isn't acceptable!

Darlene

dogger

08-23-2002, 12:36 AM

Karen'sMom , i never got MP at all . i've put the full circumstances in another post . basically my local Doctor wouldn't call in the Air Ambulance , so what should have been a less than 4 hour trip to hospital [ including waiting for the aircraft } turned into a 14 hour trip by road . then it was too late to bother about MP . however my specialist sent out a letter to all hospital superintendants [ doctors] outside of the state capital that air retrieval was to be used in all suspected SCI cases . this would then ensure they got MP in time . the thing that really annoys me about not getting MP is that i am an incomplete C5/6 and can walk , what extra function may have returned if i had received MP .
thank you
dogger

Wise Young

08-23-2002, 05:56 AM

The benefits of methylprednisolone are modest. If started more than 8 hours after injury, NASCIS 2 suggests that it is not only not beneficial but may reduce recovery. However, if started within 8 hours, on average, it improves motor recovery from 8% (if not treated) to 21% of what people had lost (usually 2-3 segments below the injury site) in "complete" spinal cord injury and from 59% (if not treated) to 75% of what a person with "incomplete" spinal cord injry. NASCIS 3 showed no difference between people given a bolus dose of 30 mg/kg methylprednisolone with 3 hours followed by 24 hours of 5.4 mg/kg/hour of methylprednisolone, 48 hours of 5.4 mg/kg/hour of methylprednisolone, or 6 mg/day of tirilazad mesylate (an antioxidant steroid). However, in people that were treated more than 3 hours after injury, people receiving the 48 hour course of methylprednisolone had significantly better motor recovery.

The current recommendation is that people get a 30 mg/kg bolus of methylprednisolone as soon as possible within 8 hours and a 24-hour course of the drug at 5.4 mg/kg/hour if they are treated within 3 hours, and a 48-hour course of the drug at 5.4 mg/kg/hour if they are treated between 3 and 8 hours. People who come in later than 8 hours should not be treated with the drug.

I believe that people should be decompressed as soon as possible after spinal cord injury. Many animal studies have now shown that continued compression of the cord even for an hour or two after injury greatly increases the severity of the injury. Despite that, most patients are not decompressed until several hours and many not until 24-48 hours. Many neurosurgeons have been calling for a clinical trial to compare early and late decompression to gather the evidence for the beneficial effects of early decompression so that this could be used to improve emergency transportation and staffing of level 1 trauma centers to do immediate decompression of spinal cord injury.

When I was in Indonesia, I heard a wonderful talk by a group of neurosurgeons from Budapest. What they do there really put American trauma centers to shame. They are routinely getting their patients into the operating room and definitively decompressing and stabilizing both cervical and thoracic spinal cord injury within 1-2 hours after injury. That is an amazing feat, considering the limited resources that they have. Switzerland, likewise, is another country that rapidly treats all their patients with methylprednisolone and decompression.

Wise.

Jeff

08-23-2002, 07:28 AM

The more I learn about the acute phase of SCI the more I realize why I recovered so little. If early decompression is a good thing then I was totally hosed by my neurosurgeon. I wasn't operated on until TWO WEEKS after injury. They put a halo on me right away and traction on my skull to keep my neck straight but waited a full two weeks to fix my broken neck. When they finally operated they did an anterior fusion to stabilize the vertebrae. I wonder if I was definitively decompressed or not.

I was hurt June 12, 1980. It was still a very dark age for SCI.

~See you at the SCIWire-used-to-be-paralyzed Reunion http://www.stopstart.fsnet.co.uk/smilie/wavey.gif ~

Emi2

08-23-2002, 09:51 AM

where I wa brought after my crash my doctor started MP, and I was on it for about 8 hours while I waited for the Air Ambulance to come and fly me to a larger center. As soon as I as brought to the emergency here in Edmonton the doctor commented that MP 'was only used in rural areas' and disconnected my IV....

Karen'sMom

08-23-2002, 10:35 AM

Emi,

That's awful that your Edmonton Doctor disconnected your IV for MP. I am glad that you at least received it for 8 hours immediately after your accident. Surely that must have helped somewhat......I hope it did.

Dogger,

I DID read about your horrifying ambulance situation. Terrible! It is unbelievable in this day and age that this could happen. I also wonder what other functions my daughter, Karen, would have gotten back as she is walking with AFO and two canes.

Wise,

Now I find out that if MP started MORE than 8 hours after injury it MAY reduce recovery......Yikes!

Karen's Doctor delayed her surgery for 24 hours after she finished the 24 hours of MP, so it would be out of her system. He also didn't want to do the surgery earlier because her Spinal Cord area was so swollen. She had her surgery three days after her injury. Now it seems that the sooner the surgery is done, the better. I am very grateful for all the recovery Karen has made so far (she is still in outpatient rehab making progress), but it is hard to accept that maybe she would even have more recovery, if things were done differently. Does anyone with SCI "ever" have a "complete" recovery?

Thanks,

Darlene

Sue Pendleton

08-23-2002, 09:25 PM

Isn't there some evidence now that MP can help even after the 8 hour window? I understand that that is not considered a major problem for those with suspected transverse myelitis, MS exacerbations and a few other central nervous system problems. I believe the severity of the injury has something to do with the window of opportunity to a certain extent.

Max

09-02-2002, 12:12 PM

Moreover there are other very inexpecive methods to protect spine & brain after injury-like oxygen/hyparbaric (pardon my French:) chambers & cooling spine & brain after injury...But nobody does apply them in US and Canada.

Sometimes I think there is a conspiracy to put & keep us in chairs http://sci.rutgers.edu/forum/images/smilies/mad.gif

==============================
"Experience teaches that, of all the emotions, fear stands alone in its power to move us, or to capture us in its grip forever. In a world of terrors, there is nothing more fearsome that the unknown...especially when what is unknown is ourselves." Outer Limits(Fear Itself)

Wise Young

09-02-2002, 12:40 PM

Max, hyperbaric chambers are not cheap. Just the oxygen and the pressure chambers alone cost more than an ICU bed. But, more important, the evidence that hyperbaric treatment is beneficial for traumatic spinal cord injury is limited, unless of course there is continued compression and ischemia of the spinal cord. Since about half of the doctors don't seem to believe or care that the spinal cord is compressed for days or even weeks after injury, thinking that if a person is "complete", there is no reason to hurry. If ignorance can be called conspiracy, I agree with you. For nearly 20 years I have been trying to speak out on the subject of early decompression and it has not had much effect. If even early decompression is not accepted as goal, why should hyperbaric treatments be? It is enormously frustrating. I don't think that it is a conspiracy unless you believe that ignorance is a conspiracy.

Wise.

Max

09-02-2002, 12:57 PM

I agree chambers are expensive, but what about cooling brain & spine after injury??

Every year I see articles about it, & yet its not widely applied. In rehab I saw
a walking high quad C4 who had car crush in winter & spend time almoust frozen, but it prserved his ability to walk

==============================
"Experience teaches that, of all the emotions, fear stands alone in its power to move us, or to capture us in its grip forever. In a world of terrors, there is nothing more fearsome that the unknown...especially when what is unknown is ourselves." Outer Limits(Fear Itself)

Red_1 Canada

09-02-2002, 03:54 PM

I am five months post injury...t-10 complete.
I have started going into a chamber as of two weeks ago.
I am planning to do 100 sesions at a total cost of 10,000 cdn$.
I have only done 14 trestments so far and have not noticed much diiference.
The one thing I have notticed is that when I am crawling out of the chamber after the treatment my legs fight me every "step" of the way...my spasums are increased. I think this is probably just because they have more energy in them.
I don't know if it is goin gto help but I am probably going to do all 100
sessions.
The cost is deffinatly a down side but its all I can do right now...and I want to be doing something.

chasb

09-02-2002, 06:56 PM

I'm not a doctor, but I feel you could put your money to better use. I too tried hyperbaric treatments (3 weeks worth). Obviously it's your choice. If you bought an excercise bike and a stim you would probably be better off. Just my thoughts.

Max

02-27-2005, 08:54 PM

"However, one-quarter of surgeons do not administer steroids at all. Of those who administer methylprednisolone, most do so because of peer pressure or out of fear of litigation. Conclusions: The vast majority of spine surgeons in Canada either do not prescribe methylprednisolone for acute SCI, or do so for what might be considered the wrong reasons. These results demonstrate the need for an evidence-based practice guideline. The Candian Spine Society and the Canadian Neurosurgical Society fully endorse the recommendations of the steroid task force (see preceding paper)."

http://stores.ebay.com/MAKSYM-Variety-Store

Wise Young

02-27-2005, 09:55 PM

Max, are you bumping this 2002 paper up for a reason? It is sad because of this paper that most people in Canada may be deprived of the benefits of methylprednisolone. In the United States, most neurosurgeons give the NASCIS II methylprednisolone dose to people with spinal cord injury. At least four randomized clinical trials and many animal studies have indicated that the drug improves recovery after spinal cord injury. Dr. Hurlburt provides no new evidence of any sort and his paper is filled with misleading statements about the clinical trial. If Dr. Hurlburt believes in "evidence-based practice guidelines" perhaps he should provide some evidence that counters the data. If his critique of the use of methylprednisolone were applied to other neurosurgical practices, neurosurgeons would have very little to do since a majority neurosurgical practices have less or no randomized clinical trial evidence that support their safety or efficacy. By the way, I happen to think that Dr. Hurlburt is a very good neurosurgeon. I just disagree with him on this issue.

Wise.

Susan Fajt

02-27-2005, 11:15 PM

http://sci.rutgers.edu/forum/images/smilies/frown.gif- i received methylprednisolone?

Godspeed~
Susan
www.sciwalker.com (http://www.sciwalker.com)

[This message was edited by Susan Fajt on 02-28-05 at 03:04 AM.]

Max

04-29-2008, 05:48 PM

Sorry Wise to pee;) on your parade!

You are mon ami;) but truth is important.

METHYLPREDNISOLONE REVISITEDLaurance Johnston, Ph.D.
http://www.healingtherapies.info/_themes/copy-of-industrial/indhorsd.gif
Methylprednisolone (MP) is a glucocorticoid steroid (illustration) administered soon after spinal cord injury (SCI) in an effort to minimize neurological damage. If you have sustained a SCI over the past dozen years or so, you were probably treated with this drug. Although it has become a de facto post-injury standard of care in the U.S., many scientists are challenging MP’s effectiveness and underlying scientific foundation. http://www.healingtherapies.info/MP_small.jpg (http://www.healingtherapies.info/MP.jpg)

http://www.healingtherapies.info/MP.htm

Do you use methylprednisolone for acute spinal cord injury?

http://www.healingtherapies.info/MP.htm

And here most damaging

The problem of lack of access to underlying data, rather than just authors’ conclusions, has concrete and worrying effects, says Fred Geisler, a neurosurgeon at the Illinois Neuro-Spine Center. Geisler points to the use of high dose steroids in spinal injury patients on the basis of a single, potentially flawed study funded by the National Institutes of Health (NIH).8 (http://www.bmj.com/cgi/content/full/336/7643/532#REF8) Geisler calculates that several thousand patients have died as the result of high dose steroids used to treat acute spinal cord injury. Two recent surveys show that most neurosurgeons agree with him.9 (http://www.bmj.com/cgi/content/full/336/7643/532#REF9) They believe that steroids are either useless or dangerous; yet when asked why most of them continue to give the drug, they cite fears of malpractice on the basis of the standard of practice set by the NIH study. Several researchers have lobbied unsuccessfully for the release of the underlying data, without which they cannot verify their concerns—or lay them to rest.9 (http://www.bmj.com/cgi/content/full/336/7643/532#REF9)

http://www.bmj.com/cgi/content/full/336/7643/532

Regards

Wise Young

04-30-2008, 03:19 AM

No pee on my parade. It is sad that the people who have been criticizing methylprednisolone have themselves produced no credible data to challenge the clinical trials that have been done. Finally, if they really believe that methylprednisolone is ineffective, it would be the ideal placebo drug against which they can show that another therapy is better. Wise.

Sorry Wise to pee;) on your parade!

You are mon ami;) but truth is important.

METHYLPREDNISOLONE REVISITEDLaurance Johnston, Ph.D.
http://www.healingtherapies.info/_themes/copy-of-industrial/indhorsd.gif
Methylprednisolone (MP) is a glucocorticoid steroid (illustration) administered soon after spinal cord injury (SCI) in an effort to minimize neurological damage. If you have sustained a SCI over the past dozen years or so, you were probably treated with this drug. Although it has become a de facto post-injury standard of care in the U.S., many scientists are challenging MP’s effectiveness and underlying scientific foundation. http://www.healingtherapies.info/MP_small.jpg (http://www.healingtherapies.info/MP.jpg)

http://www.healingtherapies.info/MP.htm

Do you use methylprednisolone for acute spinal cord injury?

http://www.healingtherapies.info/MP.htm

And here most damaging

The problem of lack of access to underlying data, rather than just authors’ conclusions, has concrete and worrying effects, says Fred Geisler, a neurosurgeon at the Illinois Neuro-Spine Center. Geisler points to the use of high dose steroids in spinal injury patients on the basis of a single, potentially flawed study funded by the National Institutes of Health (NIH).8 (http://www.bmj.com/cgi/content/full/336/7643/532#REF8) Geisler calculates that several thousand patients have died as the result of high dose steroids used to treat acute spinal cord injury. Two recent surveys show that most neurosurgeons agree with him.9 (http://www.bmj.com/cgi/content/full/336/7643/532#REF9) They believe that steroids are either useless or dangerous; yet when asked why most of them continue to give the drug, they cite fears of malpractice on the basis of the standard of practice set by the NIH study. Several researchers have lobbied unsuccessfully for the release of the underlying data, without which they cannot verify their concerns—or lay them to rest.9 (http://www.bmj.com/cgi/content/full/336/7643/532#REF9)

http://www.bmj.com/cgi/content/full/336/7643/532

Regards

Max

04-30-2008, 05:25 PM

Subject: Spinal cord steroids in children....
Date: Thu, 13 Nov 2003 11:44:44 -0500
From: Perry W. Stafford
Please forgive the following preamble, but I'm in the midst of preparing for a deposition concerning a 2 month old unrestrained child in an MVC who unfortunately had a severe CHI and was transported to us 7 hours postinjury intubated with sedation and paralysis and well resuscitated with adequate cervical spine stabilization (well taped to towel rolls and on a peds spine board aligned appropriately)....we were concerned about the baby's minimal movement of the extremities as the baby began to wake up here....cervical spine xrays and a CTScan of the cervical spine were normal....SCIWORA (spinal cord injury without radiographic abnormality) was suspected, and spinal steroids were ordered and finally started 9 hours post-injury (2 hours after arrival here)....an MRI showed a ligamentous injury with a cord contusion....despite good resuscitation of the baby, the brain, and the spinal cord, the baby is paraplegic...I'm being deposed in a suit alledging that the 2 hour delay in the start of spinal steroids after transfer from the outlying hospital contributed to the child's eventual outcome.....nonsense, but does anyone know the final outcome of the ongoing neurosurgical discussions about the Bracken protocol...I recall that we have been told that the neurosurgeons were thinking of changing their protocol suggestions concerning the use of steroids in non-penetrating spinal cord injury, but I cannot find what if anything came out of this....there is very little/nothing in our pediatric literature reflecting the efficacy of spinal steroids, and we have been extrapolating the indications and protocol from the adult literature, which has been controversial and somewhat contentious....anyone have any updates on the adult literature concerning spinal cord steroid protocols...appreciate your comments...

http://www.hwbf.org/hwb/conf/perr1/pedster.htm

Date: Fri, 14 Nov 2003 18:07:04 -0500
From: carl hauser
Here's another.
Nesathurai S., J Trauma. 1998 Dec;45(6):1088-93.
Steroids and spinal cord injury: revisiting the NASCIS 2 and NASCIS 3 trials.
The National Acute Spinal Cord Injury Study (NASCIS) 2 and 3 trials are often cited as evidence that high-dose methylprednisolone is an efficacious intervention in the management of acute spinal cord injury. Neither of these studies convincingly demonstrate the benefit of steroids. There are concerns about the statistical analysis, randomization, and clinical end points. Even if the putative gains are statistically valid, the clinical benefits are questionable. Furthermore, the benefits of this intervention may not warrant the possible risks. This paper comments on these two clinical trials.

shak

05-01-2008, 01:53 AM

Wise Young

05-01-2008, 06:36 AM

Max,

Four randomized multicenter clinical trials involving many hundreds of patients have shown that methylprednisolone improves function in people with acute spinal cord injury. The evidence that methylprednisolone does not work is based on several retrospective (i.e. non-randomized) studies and one small single-center trial that randomized 100 patients to four treatments (calcium channel blockers and methylprednisolone). Most of the data used to argue against the NASCIS (National Acute Spinal Cord Injury Study) trials were biased. Let me explain.

First, all except one of the opposing studies were non-randomized and could have been biased by the rationale of doctors to use or not use methylprednisolone. Several analyses have suggested that doctors are more likely to use methylprednisolone for severe spinal cord injury than for incomplete spinal cord injury. As you know, this would seriously bias any results of non-randomized studies.

Second, none of the opposing studies have segregated analyses of complete and incomplete spinal cord injury. As you know, this is a crucial factor in comparing results. A person with incomplete spinal cord injury often will recover much more than a person with complete spinal cord injury. In a small sample of say 100 patients, half of which were treated with MP and half not, the inclusion of just 4-5 more incomplete patients into the untreated group could easily bias the results to make outcomes not significantly different.

I am amazed by people criticizing the NASCIS studies. They have been answered over and over again and yet they continue to repeat the criticism. For example, they claim that the results of the study were based on "post-hoc" analyses. This is not true. The trial was designed to test the hypotheses that earlier treatment would be better than late therapy and that MP would be have more benefit in patients with incomplete injury than those with complete. Our trials confirmed the first hypothesis and rejected the second. We cound that patients treated within 8 hours did show benefit but patients treated more than 8 hours after injury did not. Patients with complete spinal cord injury benefited from the treatment as did patients with incomplete injury. Of course, the beneficial effects were different (which is why the two groups must be compare separately) but nevertheless significant. Finally, I reject the claim that the treatments are statistically significant but not clinically significant. Clinicians and people with spinal cord injury know that a 5 point improvement in motor score is both clinically and functionally significant. If you got back your triceps, your hands, or hip flexors, the treatment is worthwhile. More important, we have to understand that the 5-point improvement is just the average. Some patients recovered 10 or more points. Some patients walked as a result of the therapies.

Some criticisms of NASCIS 2 were based on our outcome measures, saying that we use neurological outcome but did not evaluate functional outcome. I must say that this is not only unfair but the critics don't know what they are talking about. NASCIS 2 was carried out in 1985-1989. There were *no* validated functional outcome scale at the time. We developed and used the only validated outcome measure for spinal cord injury for the NASCIS 1 and 2 trials. This was later improved and adopted by the American Spinal Injury Association (ASIA) that was used in NASCIS 3. Note that we adopted the FIM scale as a functional outcome in NASCIS 3 and that trial showed a stastistically significant gain in function associated with early (<3 hour) treatment with methylprednisolone compared with late (>3 hour) methylprednisolone treatment.

Finally, as I pointed out many times, the critics have an obligation to come out some evidence of their own. For example, none of the NASCIS trials addressed the efficacy of methylprednisolone in children or gunshot wounds. This needs to be done. If the critics really think that MP is not effective in patients, they should carry out a double-blind randomized clinical trials and publish the results. That is the way science is done. If they want to have evidence-based medicine, they need to come up with the evidence. Otherwise, it is just talk.

Wise.

Subject: Spinal cord steroids in children....
Date: Thu, 13 Nov 2003 11:44:44 -0500
From: Perry W. Stafford
Please forgive the following preamble, but I'm in the midst of preparing for a deposition concerning a 2 month old unrestrained child in an MVC who unfortunately had a severe CHI and was transported to us 7 hours postinjury intubated with sedation and paralysis and well resuscitated with adequate cervical spine stabilization (well taped to towel rolls and on a peds spine board aligned appropriately)....we were concerned about the baby's minimal movement of the extremities as the baby began to wake up here....cervical spine xrays and a CTScan of the cervical spine were normal....SCIWORA (spinal cord injury without radiographic abnormality) was suspected, and spinal steroids were ordered and finally started 9 hours post-injury (2 hours after arrival here)....an MRI showed a ligamentous injury with a cord contusion....despite good resuscitation of the baby, the brain, and the spinal cord, the baby is paraplegic...I'm being deposed in a suit alledging that the 2 hour delay in the start of spinal steroids after transfer from the outlying hospital contributed to the child's eventual outcome.....nonsense, but does anyone know the final outcome of the ongoing neurosurgical discussions about the Bracken protocol...I recall that we have been told that the neurosurgeons were thinking of changing their protocol suggestions concerning the use of steroids in non-penetrating spinal cord injury, but I cannot find what if anything came out of this....there is very little/nothing in our pediatric literature reflecting the efficacy of spinal steroids, and we have been extrapolating the indications and protocol from the adult literature, which has been controversial and somewhat contentious....anyone have any updates on the adult literature concerning spinal cord steroid protocols...appreciate your comments...

http://www.hwbf.org/hwb/conf/perr1/pedster.htm

Date: Fri, 14 Nov 2003 18:07:04 -0500
From: carl hauser
Here's another.
Nesathurai S., J Trauma. 1998 Dec;45(6):1088-93.
Steroids and spinal cord injury: revisiting the NASCIS 2 and NASCIS 3 trials.
The National Acute Spinal Cord Injury Study (NASCIS) 2 and 3 trials are often cited as evidence that high-dose methylprednisolone is an efficacious intervention in the management of acute spinal cord injury. Neither of these studies convincingly demonstrate the benefit of steroids. There are concerns about the statistical analysis, randomization, and clinical end points. Even if the putative gains are statistically valid, the clinical benefits are questionable. Furthermore, the benefits of this intervention may not warrant the possible risks. This paper comments on these two clinical trials.

Max

05-01-2008, 09:16 PM

Max

05-01-2008, 09:52 PM

boy i dig this answer.

Digger was pc game I was fanatic before sci:)

Unfortunately I haven't found either Digger nor Perestroika (oh miss that one dearly) games compatible with fast nowadays comps:(

Seems like my previous, able bodied life was a dream!

Max

05-07-2008, 10:52 AM

Visiting Lecture Series Underway

Sponsored by The Miami Project and the University of Miami School of Medicine, the Gail F. Beach Memorial Visiting Lectureship will run from October 2002 to May 2003. Respected neuroscientists from other universities throughout the world are slated to present their research findings to University of Miami research faculty and students.
http://www.themiamiproject.org/Images/newsletters/the_project/nl0301/Page%204A1-%20visiting%20lecturer.jpgDr. R. John Hurlbert, (right) answers the questions of Lawrence Moon, Ph.D., post-doctoral fellow, and Alberto Pinzon, M.D., graduate student.

Initiating this year's series was R. John Hurlbert, M.D. from the University of Calgary, Foothills Hospital, Alberta, Canada. Dr. Hurlbert shared his review and interpretation of the course of clinical studies conducted on the drug methylprednisolone in his talk entitled, AMethylprednisolone for Acute SCI: Taking Down a Standard of Care.@ In the United States, methylprednisolone had become a standard of care for acute SCI. Spurred by the work of Dr. Hurlbert and his colleagues, the American Association of Neurological Surgeons is now reconsidering this standard and has developed guidelines for steroid treatment in new injuries.

http://www.themiamiproject.org/x559.xml

Wise Young

05-08-2008, 12:24 AM

You know I'm not "politcally correct";)lol in the way Western society tries to train its plebs;) and I'm not good at sophisicated "mumbo jumbo" disputes...but I'm just a stubborn Ukrainian peasant:)

So here it goes...

How would you comment fact that even your former NYU comrads:confused: ;) are critisizing use Methylprednisolone in acute injury in recent April 2, 2008 article?

I remember you were always said how good peer review is?:confused: I might be missing something here, or am I?..Anyway -you can always blame it on my valium:D ...Sigh ...I've been with you more, now, on different forums (almost 13 years), than with my ex.

I'm pointing at, in particular, to article by Dr. Sanford M. Miller published on April, 02 , 2008 in journal of Neurosurgical anesthesiology...See attached article.in pdf format..

Could it be just envy of your comrads or Tarnished Standart, you so eagerly defending?

I know that methilpredinosolone was your beloved child and one of foundations on which your rep was build, as most prominent neuro researchers of the year (I might have that Time mag somewhere)

As usual-nothing personal, I'm questioning ideas and perspective ideas of person behind them not a person;) who build career and fame on them.

Anyway it could be just too much ado 'bout nothing or someone wants to ruin you?

Max,

It is unfortunate that people who are writing these articles have not produced any new evidence to suggest that the evidence that had been collected to date is wrong. To my knowledge, John Hurlbert has never done any study on methylprednisolone but is criticizing it based on incorrect assumptions that he is making regarding the NASCIS clinical trials. All the criticisms that have been made against the NASCIS trials have been answered over and over again and they just ignore them and repeat the criticism.

I don't understand what it is that you don't understand about what I have said. Would you like to understand and discuss it or are you just going to post all these negative attacks without trying discuss the basis for the criticism? They are not so hard. If you would like, I would be glad to discuss the details of the Sanford M. Miller paper but only with the proviso that you (or others) are interested in the details instead of hiding behind the pretense that this is not "personal" and that you don't or can't understand the science behind the studies.

Wise.

Sue Pendleton

05-08-2008, 12:38 AM

Max, you might also want to do some searches about steroid use in children as young as 12 months for non-traumatic TM. When TM effects young children it is almost always at the cervical level. A review study may be possible but no one would do a double blind study on toddlers when ventilators are/were the norm.

Max

05-09-2008, 02:29 AM

Max,

It is unfortunate that people who are writing these articles have not produced any new evidence to suggest that the evidence that had been collected to date is wrong. To my knowledge, John Hurlbert has never done any study on methylprednisolone but is criticizing it based on incorrect assumptions that he is making regarding the NASCIS clinical trials. All the criticisms that have been made against the NASCIS trials have been answered over and over again and they just ignore them and repeat the criticism.

I don't understand what it is that you don't understand about what I have said. Would you like to understand and discuss it or are you just going to post all these negative attacks without trying discuss the basis for the criticism? They are not so hard. If you would like, I would be glad to discuss the details of the Sanford M. Miller paper but only with the proviso that you (or others) are interested in the details instead of hiding behind the pretense that this is not "personal" and that you don't or can't understand the science behind the studies.

Wise.

Wise,

I'm just reposter monkey;)

Yes, I do sometime upleasant comments...

But I don't see your comments about articles, in my opinion damaging your reputation in scientific magasines...Where you can find equal opponents!

Do you really think I shoud get a degree in biology?..Just to conquer/oppose you?...I ain't marching anymore (Phil Okcs)

You are silly man;) if you think so...you got other bunch of peopla-to think way you do

Things about MP reapear somehow miraculously-sure I will stop commenting on them and about 4-Ap..Is this still a free website, or isn't it?

Ask yourself why practicing neurosurgereons are Questioning MP?

They seem to have nothing to gain?..Its well known fact -In US and Canada-that practicing Drs. are in cohuts:) with each other, no one will dare to testify in court agaist others malpractice...You know powerful Unions--So do those voices conspired again MP?...I bet more to come..

Continue rubbing shoulders with powerful ones???...one day it might or might not work for you..time will tell.esc versus adult!

With all my respect

I do post/repost everyting I find useful-to make people think

Thank you,

Max

cali

05-09-2008, 02:38 AM

dude, i'm gonna have to refer to talladega nights here and say:

you can't say whatever you want then say with all respect. well, i lie. you can, but it's stupid considering he deserves more respect than what you just gave him. unlike you, he practiced restraint replying to you.

*sigh* guess i ought to do the same. i'm out. shame! but i'm out.

chasb

05-09-2008, 05:45 AM

If methylprednisolone poses a considerable risk to the patients, perhaps the criticism would be justified. However, to date, there has not been any convincing evidence that a 30 mg/kg bolus of methylprednisolone followed by 23 hours of 5.4 mg/kg/hour increases morbidity or mortality after spinal cord injury. Over the past 10 years, probably over a million people have received this treatment (methylprednisolone is not only use for spinal cord injury but for multiple sclerosis). If the drug has serious side-effects, it certainly would have been reported by now.

Wise.

Max,

You continue to repost information, you are beating a dead horse. Go outside and get some oxygen, take a break from posting for a while.

Due to my injury, I have conducted quite a bit of research information. In my opinion, methylprednisolone is the only drug to date that provides a benefit to the spinal cord injured patient, with negligible risk.

If I lived in Canada (or anywhere else) and was denied methylprednisolone during a spinal cord injury treatment by any physician, I would look into filing suit against the physician and the hospital for malpractice.

wildwilly

05-09-2008, 06:01 AM

I have heard numerous Doc's make arguments or vocalize concerns over the use of MP. It would be nice if they would come to this site for a legitimate scientific debate about MP. I personally do not understand how critics continue to make retrospective reviews/analysis of the NASCI trials. I say move forward with MP research (or other compounds) and produce some new data. The knowledge of why/how something did/did not work is valuable (not necessarily that it had a positive/negative/significant/insignificant effect). Below is an abstract on the potential mechanism of MP.

J Neurosci. 2008 Mar 19;28(12):3141-9.

Methylprednisolone protects oligodendrocytes but not neurons after spinal cord injury.

Lee JM, Yan P, Xiao Q, Chen S, Lee KY, Hsu CY, Xu J.

The Hope Center for Neurological Disorders and Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Methylprednisolone (MP) is used to treat a variety of neurological disorders involving white matter injury, including multiple sclerosis, acute disseminated encephalomyelitis, and spinal cord injury (SCI). Although its mechanism of action has been attributed to anti-inflammatory or antioxidant properties, we examined the possibility that MP may have direct neuroprotective activities. Neurons and oligodendrocytes treated with AMPA or staurosporine died within 24 h after treatment. MP attenuated oligodendrocyte death in a dose-dependent manner; however, neurons were not rescued by the same doses of MP. This protective effect was reversed by the glucocorticoid receptor (GR) antagonist (11, 17)-11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one (RU486) and small interfering RNA directed against GR, suggesting a receptor-dependent mechanism. MP reversed AMPA-induced decreases in the expression of anti-apoptotic Bcl-x(L), caspase-3 activation, and DNA laddering, suggesting anti-apoptotic activity in oligodendrocytes. To examine whether MP demonstrated this selective protection in vivo, neuronal and oligodendrocyte survival was assessed in rats subjected to spinal cord injury (SCI); groups of rats were treated with or without MP in the presence or absence of RU486. Eight days after SCI, MP significantly increased oligodendrocytes (CC-1-immunoreactive cells) after SCI, but neuronal (neuronal-specific nuclear protein-immunoreactive cells) number remained unchanged; RU486 reversed this protective effect. MP also inhibited SCI-induced decreases in Bcl-x(L) and caspase-3 activation. Consistent with these findings, the volume of demyelination, assessed by Luxol fast blue staining, was attenuated by MP and reversed by RU486. These results suggest that MP selectively inhibits oligodendrocyte but not neuronal cell death via a receptor-mediated action and may be a mechanism for its limited protective effect after SCI.

http://www.ncbi.nlm.nih.gov/pubmed/18354017?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVDocSum

Max

05-09-2008, 03:11 PM

Steroids in SCI: Take a stand

Bjorn, Pret pbjorn at emh.org (trauma-list%40trauma.org?Subject=Steroids%20in%20SCI%3A%2 0Take%20a%20stand%20&In-Reply-To=)
Wed Oct 27 13:16:15 BST 2004

Previous message: trauma-list Digest, Vol 16, Issue 34 (http://list.mistral.net/pipermail/trauma-list/2004-October/023210.html)
Next message: Trauma Care and Telerad (http://list.mistral.net/pipermail/trauma-list/2004-October/023211.html)
Messages sorted by: [ date ] (http://list.mistral.net/pipermail/trauma-list/2004-October/date.html#23212) [ thread ] (http://list.mistral.net/pipermail/trauma-list/2004-October/thread.html#23212) [ subject ] (http://list.mistral.net/pipermail/trauma-list/2004-October/subject.html#23212) [ author ] (http://list.mistral.net/pipermail/trauma-list/2004-October/author.html#23212)The Maine EMS Trauma Advisory Committee (TAC) yesterday approved a publicrecommendation to the state EMS Board of Directors regarding the use ofsteroids in acute spinal cord injury. The language is as follows:"The Maine Trauma Advisory Committee recommends, after reviewing currentliterature, that methylprednisolone sodium succinate (MPSS) not berecommended therapy for acute spinal cord injury (ASCI). We furtherrecommend against its use in the prehospital or community hospital setting.The use of MPSS should only be considered as a treatment option at theregional trauma centers."Say what you will about the tone and word selection; the TAC is an advisorycommittee only, and is fully aware of the clinical and cultural controversyattached to steroids in cord injury. As a language buff, I'm queasy overrecommending that something not be recommended, and it strikes me that theword "further" might well be replaced with "specifically." But it's astart.http://list.mistral.net/pipermail/trauma-list/2004-October/023212.html

shelley

05-09-2008, 03:48 PM

Max,

If I lived in Canada (or anywhere else) and was denied methylprednisolone during a spinal cord injury treatment by any physician, I would look into filing suit against the physician and the hospital for malpractice.

My husband was treated in a major Toronto Hospital that provides "world-class care" in Neuroscience. He was not given methylprednisolone, nor was it even put forth as an option. Of course he wasn't aware of what was happening, and I wasn't aware of methylprednisolone until well after it would have been beneficial.

Once I did know, and questioned his doctor, I was told that the risks would have far out-weighed the benefits. That was five years ago. I was hopping mad, but I don't think a law suit would go anywhere here in Canada.

I don't know if it would have helped my husband or not, but knowing what I know now and what he has been through ~ ANYTHING would have been worth the risk.

Sue Pendleton

05-09-2008, 04:00 PM

Max, can you find the current cost of the normal amount of MPSS used in acute SCI cases in the major western countries? I believe it's still under the brand name Solumedrol in most places.

Max

05-09-2008, 05:16 PM

Max, can you find the current cost of the normal amount of MPSS used in acute SCI cases in the major western countries? I believe it's still under the brand name Solumedrol in most places.

Here it is Government of India

http://nppaindia.nic.in/ceiling/press21jun02/21-6-02-pharmacia.html

Methylprednisolone. Solu-Medrol. Anti-inflammatory. Bedford Labs (http://www.bedfordlabs.com/products/ViewProductDetails?brand=Solu-Medrol)Methylprednisolone. Brand Name / Company Solu-Medrol Pfizer. Therapeutic Class Anti-inflammatory ... Preservative Free, WAC Price. Yes, USD25.00 ...

Here 1 gram 104.35$

http://www.rxtank.com/products.php?alpha=Solu%20Medrol

Sorry Sue-I'm unable to find curent case, ammount & price involved into treating acute sci:( Maybe Dr. Young knows

Max

05-09-2008, 07:09 PM

Methylprednisolone for acute spinal cord injury: not a standard of care

Herman Hugenholtz
Dr. Hugenholtz is with the Division of Neurosurgery, Queen Elizabeth II Health Sciences Centre, Halifax, NS.Members of the Committee of the Canadian Spine Society and the Canadian Neurosurgical Society to Review the Role of Methylprednisolone in Acute Spinal Cord Injury: Herman Hugenholtz (chair), Division of Neurosurgery, Queen Elizabeth II Health Sciences Centre, Halifax, NS; Nirmala D. Bharatwal, Toronto Rehabilitation Institute, Toronto, Ont.; Dan E. Cass, Director of Emergency Services, St. Michael's Hospital, Toronto, Ont.; Marcel F. Dvorak, Medical Director, Combined Spine Program, Vancouver Hospital and Health Sciences Centre, Vancouver, BC; Derek Fewer, Section of Neurosurgery, Health Sciences Centre, Winnipeg, Man.; Richard J. Fox, Department of Neurosurgery, Walter C. Mackenzie Health Science Centre, University Hospital, Edmonton, Alta.; Dennis M.S. Izukawa, Department of Neurosurgery, Trillium Health Centre, Mississauga, Ont.; Joel Lexchin, Emergency Department, University Health Network, Toronto, Ont.; Christine Short, Nova Scotia Rehabilitation Centre, Halifax, NS; and Sagun Tuli, Department of Neurosurgery, Brigham and Women's Hospital, Boston, Mass.
Correspondence to: Dr. Herman Hugenholtz, New Halifax Infirmary, Rm. 3808, 1796 Summer St., Halifax NS B3H 3A7; fax 902 473-8912
It is time to clear the confusion about the utility of steroids in cases of acute spinal cord injury. A committee of Canadian neurosurgical and orthopedic spine specialists, emergency physicians and physiatrists (listed at the end of the article) has reviewed the evidence and concluded that high-dose methylprednisolone infusion is not an evidence-based standard of care for patients with such an injury.1 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R1-21)
The consequences of a spinal cord injury are often devastating, and any possibility of mitigating neurologic loss is attractive. To this end, management of acute spinal cord injuries has included the use of steroids for the past 30 years, based in large part on physiological hypotheses with limited clinical support.2 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R2-21),3 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R3-21) Mechanical injury to the spinal cord initiates a cascade of secondary events that include ischemia, inflammation and calcium-mediated cell injury. Animal experiments have shown that methylprednisolone exhibits potential neuroprotective effects through its inhibition of lipid peroxidation and calcium influx and through its anti-inflammatory effects.4 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R4-21),5 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R5-21) Three well-designed, large, randomized clinical trials (the National Acute Spinal Cord Injury Studies [NASCIS I, II and III]) examined the effect of steroid administration in patients with acute spinal cord injury.6 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R6-21),7 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R7-21),8 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R8-21),9 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R9-21),10 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R10-21),11 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R11-21)
NASCIS I examined the change in motor function in specific muscles and changes in light touch and pinprick sensation from baseline.6 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R6-21),7 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R7-21) The study detected no benefit from methylprednisolone, but the dose was considered to be below the therapeutic threshold determined from animal experiments. Therefore, NASCIS II used a much higher dose, and patients were randomly assigned to receive a 24-hour infusion of methylprednisolone, naloxone or placebo within 12 hours after acute spinal cord injury.8 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R8-21),9 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R9-21) Again, there was no benefit overall in the methylprednisolone group; however, post hoc analyses detected a small gain in the total motor and sensory score in a subgroup of patients who had received the drug within 8 hours after their injury. As a result, this 24-hour, high-dose methylprednisolone infusion, if started within 8 hours after injury, quickly became an implied standard of care despite considerable criticism of the validity of such a post hoc analysis.
Subsequent clinical trials have provided conflicting evidence about steroid treatment in acute spinal cord injury. A Japanese study attempted to replicate the results seen in the 8-hour subgroup from NASCIS II and reported improved function at 6 months in a larger number of muscles and sensory dermatomes among subjects who received high-dose methylprednisolone infusion than among those who received only low doses of the drug or no drug.12 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R12-21) However, the study lacked detail about randomization and outcome measures, and it included only 74% of the enrolled subjects in the outcome analysis. Conversely, an underpowered prospective randomized trial that used a methylprednisolone regimen similar to that used in NASCIS II found no improvement in motor and sensory scores at 1 year.13 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R13-21),14 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R14-21) NASCIS III compared a 48-hour infusion of methylprednisolone with a 24-hour infusion started within 8 hours after injury and found no benefit from extending the infusion beyond 24 hours. Again, only post hoc analysis showed a benefit from extending the infusion to 48 hours when treatment was started between 3 and 8 hours after injury. No other study has verified the primary outcome of 48 hours versus 24 hours or the post hoc conclusion of benefit from starting treatment between 3 and 8 hours after injury.
A meta-analysis of all of the trials concluded, on the basis of the controversial subgroup post hoc analyses in NASCIS II and III and the data from the Japanese study, that a 24-hour high-dose methylprednisolone infusion within 8 hours after injury is efficacious.15 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R15-21) Despite this meta-analysis, the efficacy of such a regimen remains uncertain and will require further study. The controversy about the post hoc analyses of NASCIS data continues,16 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R16-21),17 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R17-21),18 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R18-21),19 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R19-21),20 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R20-21),21 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R21-21),22 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R22-21),23 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R23-21) and unfortunately the studies that could have clarified the efficacy of such a regimen have lacked the rigour to do so.
Steroid therapy is not without risk. Most patients with acute spinal cord injury are treated in intensive care units, have polytrauma, have impaired lung capacity and are vulnerable to sepsis. In all 3 NASCIS studies and other, smaller studies, the incidence of sepsis and pneumonia was higher in the high-dose methylprednisolone groups than in the placebo or other treatment groups;6 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R6-21),7 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R7-21),8 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R8-21),9 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R9-21),10 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R10-21),11 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R11-21),24 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R24-21),25 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R25-21),26 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R26-21) the differences were not significant except in NASCIS III. Hyperglycemia and gastrointestinal complications were also reported following high-dose methylprednisolone treatment.13 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R13-21),24 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R24-21) Therefore, it has been proposed that, without compelling evidence for its efficacy, methylprednisolone should be used with caution and may even be harmful, particularly if infusion goes beyond 24 hours.17 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R17-21)
The cost of a 24-hour methylprednisolone infusion is not prohibitive, and a gain of antigravity strength in one or more muscles below a spinal segment can provide an important functional gain, especially for patients with cervical spinal cord injuries. Therefore, even the small improvement observed in the NASCIS subgroups could be viewed as a benefit in cases of complete or incomplete cervical cord injury. Despite the risk of complications and as long as the outcomes in the NASCIS subgroups remain a possibility, physicians may still opt to administer a high-dose methylprednisolone infusion within 8 hours after injury. However, they should no longer feel compelled to do so. Physicians who conduct the initial triage and resuscitation of patients with acute spinal cord injury should consult their specialist colleagues who will be continuing the care of these patients regarding their preference for methylprednisolone infusion.
The Canadian Neurosurgical Society, the Canadian Spine Society and the Canadian Association of Emergency Physicians have adopted the committee's recommendation that a high-dose, 24-hour infusion of methylprednisolone started within 8 hours after an acute closed spinal cord injury is not a standard treatment nor a guideline for treatment but, rather, a treatment option, for which there is very weak level II and III evidence.27 (http://www.cmaj.ca/cgi/content/full/168/9/1145#R27-21)

Footnotes
This article has been peer reviewed. :p
Competing interests: None declared.

wildwilly

05-09-2008, 08:51 PM

Whats your point Max? We can keep posting articles or we can debate. I'm upto the challenge.

Surg Neurol. 2008 Apr 25

Neuroprotective effects of infliximab in experimental spinal cord injury.

Kurt G, Ergün E, Cemil B, Börcek AO, Börcek P, Gülbahar O, Ceviker N.
Department of Neurosurgery, Gazi University Faculty of Medicine, 06500 Ankara, Turkey.

BACKGROUND: The aim of the study is to assess the effects of infliximab, a TNF-alpha receptor blocker, in a spinal cord clip compression injury model. METHODS: Clip compression injury model was used for producing spinal cord injury on 32 adult, male Wistar rats (Gazi University Animal Research Laboratory, Ankara, Turkey). After exposing the vertebral column between T7 and T10, total laminectomy was performed with the assistance of a high-speed drill and a surgical microscope. The dura was left intact. Spinal cord injury was performed on all rats with application of a 70-g closing force aneurysm clip for 1 minute. The rats were randomly allocated into 4 groups. Control group received no further therapy, whereas the other 3 groups received methylprednisolone (30 mg/kg intraperitoneal), infliximab (5 mg/kg subcutaneous), and a mixture of these 2 agents. All rats were killed 72 hours later, and the level of lipid peroxides in traumatized spinal cord tissue were measured as thiobarbituric acid-reactive material and determined using the method of Mihara and Uchiyama (Determination of malonaldehyde precursor in tissue by thiobarbituric acid test. Anal Biochem 1978;86(1):271-8). RESULTS: Treatment with infliximab and methylprednisolone decreased MDA levels in rats with spinal cord injury with a statistically significant difference. In addition, combined therapy achieved a more profound decrease in tissue MDA levels, which was also statistically significant. CONCLUSIONS: Infliximab is found as effective as methylprednisolone on spinal cord clip compression injury. Moreover, the combination of these 2 agents demonstrated higher efficacy suggesting a synergistic effect between these 2 agents. However, further studies regarding functional and behavioral analyses as well as biochemical markers are required.

http://www.ncbi.nlm.nih.gov/pubmed/18440605?ordinalpos=14&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVDocSum

wildwilly

05-09-2008, 08:51 PM

Max

05-09-2008, 09:31 PM

EMS Myth #5: Steroids are effective in the treatment of acute spinal cord injury

Posted: November 17th, 2005 02:08 PM EDT

For years, the role of high-dose corticosteroids in treating neurological trauma has been a controversial component of EMS practice. As paramedics in the 1970s, we routinely administered varying doses of dexamethasone (Decadron) to patients with head injuries. The theory behind its use was that the drug would decrease inflammation and swelling within the brain. The doses varied significantly based upon which medical control physician was on duty. Some physicians would order 4 mg, while others would order massive doses—up to 100 mg on some occasions. Finally, the neurosurgeons said it was not making a difference, and we stopped administering it.
History
High-dose corticosteroid therapy for the treatment of acute spinal cord injury was introduced to prehospital care in the 1980s. The recommended corticosteroid for this purpose was methylprednisolone (MP), and the doses were massive. Prior to the recommendation to use MP for acute spinal cord injury, many EMS services carried standard doses of the drug for use in severe allergic reactions and for difficult cases of asthma and chronic obstructive pulmonary disease. Few carried enough MP to treat acute spinal cord injury as recommended; thus, most systems prepared a special "spinal cord injury kit" that contained adequate quantities of the drug. However, review of pertinent studies has shown that high-dose steroid therapy benefits few, if any, spinal cord injury patients. Furthermore, the side effects and complications of such massive doses of steroids are significant and may outweigh any potential benefits.

http://publicsafety.com/article/article.jsp?id=2028&siteSection=19

Conclusion
The suggested use of corticosteroids in the treatment of acute spinal cord injury is another example of rushing to judgment by members of the medical and EMS communities. As they did with the use of tPA for ischemic stroke, the medical community changed worldwide treatment guidelines for acute spinal cord injury based upon a single study that, in retrospect, was not as strong as initially thought. Furthermore, no quality studies have been able to replicate the results of the NASCIS 2 trial, and based upon this, many organizations and experts have clearly stated that the use of steroids in the management of spinal cord injury is not a standard of care—not even a guideline for care—but only an option based on weak scientific evidence.
So, here is one more useless treatment modality we can remove from our prehospital treatment protocols. We can safely take the large quWantities of MP carried in many EMS and rescue units and return them to the pharmacy.

Max

05-09-2008, 09:37 PM

Questionnaire Survey of Spine Surgeons on the Use of Methylprednisolone for Acute Spinal Cord Injury.
Health Services Research
Spine. 31(9):E250-E253, April 20, 2006.
Eck, Jason C. DO, MS *; Nachtigall, Dean DO *; Humphreys, S Craig MD +; Hodges, Scott D. DO +

Abstract:
Study Design. A questionnaire survey.
Objective. Estimate the use and justification of the steroid protocol for spinal cord injury (SCI) patients.
Summary of Background Data. There remains significant debate over clinical benefits and potential complications of the steroid protocol for SCI patients. Methods. A survey was sent to spine surgeons requesting information on 1) specialization, 2) trauma center affiliation, 3) use of steroid protocol, 4) justification of using steroid protocol, and 5) SCI volume.

http://www.spinejournal.com/pt/re/spine/abstract.00007632-200604200-00021.htm;jsessionid=Lk3Z4wqnpJF3PGGwtT6J4QxSSyH52 RB0JvCBrvngGjgykyxLdjKg!-1696092046!181195628!8091!-1

Results. Responses were received from 305 surgeons. Fourteen (4.6%) surgeons used steroids only if initiated before their consult, 262 (85.9%) would initiate if within the accepted 8-hour timeframe, 20 (6.6%) did not use steroids at all, and 9 (3.0%) used a different protocol. Justification for steroids use: 65 improved recovery, 64 institutional protocol, 110 medicolegal reasons (!!!), and 26 did not personally initiate steroids. Eighteen surgeons listed both clinical benefit and institutional protocol, and 22 others listed both institutional protocol and medicolegal reasons.

Conclusions. The majority (90.5%) of responding surgeons used the steroid protocol; however, only 24.1% used the steroid protocol due to a belief in improved clinical outcomes.

Max

05-09-2008, 09:47 PM

Whats your point Max? We can keep posting articles or we can debate. I'm upto the challenge.

Why Do you cry Willy:p ?
Why Do you cry?:confused:
Why Willy? Why Willy ? Why Willy? Why!?:p

Note Willy ;) You putting abstracts about bloody rats;)

I'm putting nowadays articles about real people!

You don't have to be college graduate, or do you?-To see my point!

What challenge you talking about after this?:confused:

Okie -doc, Willard?:)lmao

http://www.allmoviephoto.com/photo/2003_willard_011_big.html

wildwilly

05-10-2008, 06:36 AM

Max

05-10-2008, 11:07 AM

Max, please. I'm not crying just asking you to make your point and make it clear (MP does not work? poor inclusion/exclusion critera, results/data did not have enough power? the therapeutic window is larger or smaller than stated......). I will honestly try and have a physiatrist I work closely with (specializes in SCI) respond to this thread. Obviously you do not need to have a degree to read the articles and form opinions. On the other hand it is helpful to understand statistics and experimental design. I have a decent grasp on biology/physiology but I would be taking great liberty if I said the same for statistics and or experimental design. Maybe Wise or someone else who specializes in this area could comment. I know most facilities have a director of research and statisticians who specialize in this area (not to mention IRB and other process that are designed to insure efficacy, validity, reliability...). As for human versus animal research, I try post every current research article I find that relates to SCI regardless of the subject's species.
Dear Willy,

I do appreciate your tenacity and willingness to learn about complicated problem/challenge sci represents. Moreover it shows that you have sincere,frank/genuine compassion for people you work day-to-day as physio. It also shows that you striving to look out of the box and not narrow minded, unlike many people with whom unfortunately our sci folk has to deal/meet.

Cry Willy, is verse with help of which, children in Russian kindergardens learning english, training how to pronounce sound repersented by letter "w"

It was subtle analogy, which just pooped;)lol out of my head, to your, in my opinion immature challenge to compare research done on lab rats for more than 35 years (spend gozzilions of $) and nowadays research/remarks of practicing neuro surgeons,trauma specialists, practicing MD's who have to struggle each day with question, to apply/not to apply mp to human beings...

So was my ironic comparison to Willard:D

I do regret if you took it as insult.

Its ok with you-I hope? you learning....

....But I's beyond my understanding and I'm puzzled why Dr. Young MD., reputable neuroscientist and great humanitarian, will not debate this issue with medical community-instead of picking up on messenger?

I doubt that other recearchers and practicing Drs are just conspiring to get him?....Something just wrong and fishy rotten here..:confused:.

Thank you,

P.S. All other of your questions are partly answered in my reposts and on websites, links I provided. I do that for people, like you -open minded and for those who like me paralysed from neck down-not up:) lol For all who do not blindly follow Sheppards;)

Max

05-10-2008, 11:14 AM

Research for a Cure in Spinal Cord Injury (2005)

Please take a moment to Evaluate (http://www.spinalcord.uab.edu/show.asp?durki=29178) this information so that we can provide you with additional information in the future.

What is Research
Research is a thorough scholarly or scientific study to discover new knowledge in a subject or provide a new understanding about a known subject matter. Billions of dollars are spent each year in the form of "grants" to conduct research in untold areas of health and wellness. These grants are typically used by universities and organizations throughout the United States (US) to conduct research to gain or advance knowledge in a specific area.

Research Process
The federal government is the biggest financial resource for research activities. Much of the funding is awarded by federal agencies such as the National Institutes of Health, the Center for Disease Control and Prevention and the National Institute on Disability and Rehabilitation Research, which also funds this information sheet. Typically, these and other agencies release announcements requesting that universities and organizations submit applications to conduct research. Researchers submit applications for funding. The applications will normally contain a detailed description of the proposed study, a rationale for the need of the study, how the study will be conducted, a budget outline, key personnel, study participants, and anticipated results. Peer-reviewers score the applications, and the best scores are usually funded. The researchers then conduct the studies according to their proposed applications.
Research outcomes are typically published in Peer-Reviewed Journals as a means for researchers to report their findings to other researchers. There are hundreds of journals, and each journal features articles in specific areas of medicine. These articles explain individual study methods and results along with a discussion on the impact of the study. Future researchers read the articles to avoid repeating studies that fail and build upon studies that are successful.

http://www.spinalcord.uab.edu/show.asp?durki=22508

To date, Methylprednisolone, GM-1 Ganglioside (Sygen), 4-Aminopyridine (4-AP), and Interleukin-10 have been studied. The use of Methylprednisolone after spinal cord injury is controversial. In general, studies suggest the drug is minimally significant at best. Yet, methylprednisolone continues to be widely used after injury. A multi-center study of Sygen has also shown mixed results. It showed no long-term improvement between non-treatment and treatment groups. However, treatment groups had earlier recovery than did the non-treatment group, but this benefit was only in the short-term. Also, some subgroups had improved recovery. Interleukin-10 and 4-AP offered no improvement in neurologic outcomes. Other drugs currently under investigation include Cyclohexamide, Gluamate (AMPA) Receptor Blockers, BAF, Hypothermia, and Opioid antagonists.

Max

05-10-2008, 02:54 PM

Note Author is specialist in emergency medicine! ...treating humans-not some kind of Rat doctor sucking govermnent grants.

Thank you!

Spinal Cord Injuries

Article Last Updated: Aug 8, 2006
AUTHOR AND EDITOR INFORMATION

Section 1 of 11 http://www.emedicine.com/images/arrowblank.gif http://www.emedicine.com/images/next3.gif (http://www.emedicine.com/emerg/fulltopic/topic553.htm#section~Introduction)

Authors and Editors (http://www.emedicine.com/emerg/topic553.htm#section~AuthorsandEditors)
Introduction (http://www.emedicine.com/emerg/topic553.htm#section~Introduction)
Clinical (http://www.emedicine.com/emerg/topic553.htm#section~Clinical)
Differentials (http://www.emedicine.com/emerg/topic553.htm#section~Differentials)
Workup (http://www.emedicine.com/emerg/topic553.htm#section~Workup)
Treatment (http://www.emedicine.com/emerg/topic553.htm#section~Treatment)
Medication (http://www.emedicine.com/emerg/topic553.htm#section~Medication)
Follow-up (http://www.emedicine.com/emerg/topic553.htm#section~Followup)
Miscellaneous (http://www.emedicine.com/emerg/topic553.htm#section~Miscellaneous)
Multimedia (http://www.emedicine.com/emerg/topic553.htm#section~Multimedia)
References (http://www.emedicine.com/emerg/topic553.htm#section~References)

Author: (http://www.emedicine.com/cgi-bin/foxweb.exe/screen@/em/ga?book=emerg&authorid=811&topicid=553) Donald Schreiber, MD, CM, Associate Professor of Surgery (Emergency Medicine), Stanford University School of Medicine

Donald Schreiber is a member of the following medical societies: American College of Emergency Physicians (http://www.acep.org/webportal)

Editors: Daniel J Dire, MD, FACEP, FAAP, FAAEM, Clinical Associate Professor, Department of Emergency Medicine, University of Texas-Houston; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Tom Scaletta, MD, Past-President, American Academy of Emergency Medicine; Chairperson, Department of Emergency Medicine, Edward Hospital; Assistant Professor of Emergency Medicine, Rush Medical College and Cook County Hospital; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Charles V Pollack, Jr, MD, MA, FACEP, Professor, Department of Emergency Medicine, University of Pennsylvania College of Medicine; Chairman, Department of Emergency Medicine, Pennsylvania Hospital

http://www.emedicine.com/emerg/topic553.htm

The National Acute Spinal Cord Injury Studies (NASCIS) II and III, a Cochrane review of all randomized clinical trials and other published reports, have verified significant improvement in motor function and sensation in patients with complete or incomplete SCIs who were treated with high doses of methylprednisolone within 8 hours of injury. The NASCIS II study evaluated methylprednisolone administered within 8 hours of injury. The NASCIS III study evaluated methylprednisolone 5.4 mg/kg/h for 24 or 48 hours versus tirilazad 2.5 mg/kg q6h for 48 hours. (Tirilazad is a potent lipid preoxidation inhibitor.) High doses of steroids or tirilazad are thought to minimize the secondary effects of acute SCI. In the NASCIS III trial, all patients (n = 499) received a 30-mg/kg bolus of methylprednisolone intravenously. The study found that in patients treated earlier than 3 hours after injury, the administration of methylprednisolone for 24 hours was best. In patients treated 3-8 hours after injury, the use of methylprednisolone for 48 hours was best. Tirilazad was equivalent to methylprednisolone for 24 hours.
Both NASCIS studies evaluated the patients' neurologic status at baseline on enrollment into the study, at 6 weeks, and at 6 months. Absolutely no evidence from these studies suggests that giving the medication earlier (eg, in the first hour) provides more benefit than giving it later (eg, between hours 7 and 8). The authors only concluded that there was a benefit if given within 8 hours of injury following the NASCIS trials.

The use of high-dose methylprednisolone in nonpenetrating acute SCI had become the standard of care in North America. Nesathurai and Shanker revisited these studies and questioned the validity of the results. These authors cited concerns about the statistical analysis, randomization, and clinical endpoints used in the study. Even if the benefits of steroid therapy are valid, the clinical gains are questionable. Other reports have cited flaws in the study designs, trial conduct, and final presentation of the data. The risks of steroid therapy are not inconsequential. An increased incidence of infection and avascular necrosis has been documented.
A number of professional organizations have therefore revised their recommendations pertaining to steroid therapy in SCI. The Canadian Association of Emergency Physicians is no longer recommending high-dose methylprednisolone as the standard of care. The Congress of Neurological Surgeons has stated that steroid therapy "should only be undertaken with the knowledge that the evidence suggesting harmful side effects is more consistent than any suggestion of clinical benefit." The American College of Surgeons has modified their Advanced Trauma Life Support guidelines to state that methylprednisolone is "a recommended treatment" rather than "the recommended treatment."
In a recent survey conducted by Eck and colleagues, 90.5% of spine surgeons surveyed used steroids in SCI, but only 24% believed that they were of any clinical benefit. Note that the authors discovered that approximately 7% of spine surgeons do not recommend or use steroids at all in acute SCI. The authors reported that most centers werefollowing the NASCIS II trial protocol.
Overall the benefit from steroids is considered modest at best, but for patients with complete or incomplete quadriplegia, a small improvement in motor strength in one or more muscles can provide important functional gains.
The administration of steroids remains an institutional and physician preference in spinal cord injury. Nevertheless, the administration of high-dose steroids within 8 hours of injury for all acute SCI patients is practiced by most physicians.
The current recommendation is to treat all SCI patients according to the local/regional protocol. If steroids are recommended, they should be initiated within 8 hours of injury with the following steroid protocol: methylprednisolone 30 mg/kg bolus over 15 minutes and an infusion of methylprednisolone at 5.4 mg/kg/h for 23 hours beginning 45 minutes after the bolus.
Local policy will also determine if the NASCIS II or NASCIS III protocol is to be followed.
Two North American studies have addressed the administration of GM-1 ganglioside following acute SCI. The available medical evidence does not support a significant clinical benefit. It was evaluated as a treatment adjunct after the administration of methylprednisolone.

Max

05-10-2008, 03:09 PM

Max, can you find the current cost of the normal amount of MPSS used in acute SCI cases in the major western countries? I believe it's still under the brand name Solumedrol in most places.

Sweet Sue,

I think your question will be better answered by American College of emergency Physicians. I failed to find answer. These people know it for sure.
http://www.acep.org/

adi chicago

05-10-2008, 03:48 PM

how many patients were cured 100% after a sci ?to my knowledge ...NONE....
to stop the more damage and to decompress the spinal cord using the methylprednisolone ASAP is ok but still not enough for new injured.
ps.dont belive that story about the football player[cooling bs stuff] ...his spinal cord was not damaged.....when a spinal cord is damaged the process is irreversible acording to the most neuro scientiests around the world.

Steven Edwards

05-10-2008, 09:04 PM

Max

05-10-2008, 11:07 PM

Max,

A few different teams are currently testing different treatments against methylprednisolone, with one researcher studying the molecular mechanisms underlying its benefit after SCI. I doubt the NIH would continue to fund such studies if MP wasn't effective.

Steven
Thank you, Steven-even;) For your always informative posts/remarks.
Hope you ok?
I wonder why neurosurgeons, emergency physicians and Drs involved in child trauma (TBI) are suddenly (most chat, articles, studies dated after 2000?) attacking MP?
Any thoughts you at liberty:confused: to share here?
Here what I think (and your post somehow supoorts my presumption(?)-for many years they were strugling with question-to administer/not administer mp. Now they just want to avoid trouble with new drugs? ...Yup I might be naive here
Why nobody here posted this info here before me?
Do you know cost of administering mp doses to acute sci?
I only was able to find here, related costs of administering mp, in chat of Drs ,involved With children trauma-"It is known that vital immune responses were adversely affected, that pneumonia was somewhat more prevalent, and that hospitalization was prolonged and costs therefore increased by an average of $51,504 per admission"
BTW very interesting reading (I know you able to read between lines)
http://www.hwbf.org/hwb/conf/perr1/pedster.htm

I admit I'm editing this post-I'm very slow due to painkillers:(

Also, if you at liberty to share who is/was original inventors/pattern holders of mp and who was receiving royalties all this years, otherwise benefited from mp?
I know you very knowlegible person..
If you can't say it here, just whisper to me;)
I promice not to reveal

Thank you, kindly in advance, for your always well articulated, balanced answers

Steven Edwards

05-11-2008, 01:05 PM

Max, I'm managing, thanks. Dismayed a little at this topic being beaten to death again, but otherwise okay. :)

I wonder why neurosurgeons, emergency physicians and Drs involved in child trauma (TBI) are suddenly (most chat, articles, studies dated after 2000?) attacking MP? PMS? Mid-life crisis? Who knows.

An interesting fact:

Evidence of benefit from corticosteroids in acute spinal cord injury has renewed interest in their role in brain injury. The second US national acute spinal cord injury study (NASCIS 2) compared 24 hours of corticosteroid (methylprednisolone) with placebo in 333 patients with acute spinal cord injury. At six months patients who had received corticosteroids within eight hours of injury had greater improvement in motor function and in sensation to pinprick and touch. Similar results were reported in a Japanese trial of 151 patients who received the same regimen. More recent trials of methylprednisolone in acute spinal cord injury have indicated slightly more neurological recovery with 48 than with 24 hours of treatment. On the basis of these results high dose methylprednisolone is now widely used in acute spinal cord injury. (Source (http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=10894675)) The Japanese trial also demonstrated that high-dose methylprednisolone after SCI is beneficial.

Any thoughts you at liberty to share here? Just the above. There's a good bit of point-counterpoint in various journals about methylprednisolone. A paper will come out criticizing MP for one minor point, then a rebuttal will be published showing how the criticer's analysis is flawed. I'm sure it gets tiring.

Why nobody here posted this info here before me? Come now, you don't remember Bob and Faye stirring this same nest? You're not the first to post it.

Do you know cost of administering mp doses to acute sci? Nope.

Also, if you at liberty to share who is/was original inventors/pattern holders of mp and who was receiving royalties all this years, otherwise benefited from mp? Methylprednisolone is the generic form of the drug Medrol. Nobody gets royalties for methylprednisolone purchases.

Does any of that help?

Max

05-11-2008, 03:56 PM

Thanks Steven,

I somehow missed posts of Faye and Big Bob:confused: , probably I was at hospital?...I even still clearly dont understand what crime they did to be banned?...I see many other people abusive posts-but nobody ban those people...anyway its water under the bridge now.. I even missed news about Simon Meson? Its either painkillers + valium or its sci which messing with my timeline....I was even half a year or so on that marihuana spray, it was good painkiller, but I gained weight and noticed smoking more so I stopped..Lyrica helps, but pain getting increased-I dont want to increase Lyrica.

Things that happened in begining of 2000 somehow seem to happened yesterday, things happening 2-3 month ago seem to be very distant....Somehow suddenly my little girl is grown....

Anyway I wish your mid-life-crisis suggestion could be true and only reasonable explanation...About Respectable and reputable Drs. working everyday with victims (real pepole) of sci/tbi and not with rats;)ll

Best regards

Wise Young

05-11-2008, 05:01 PM

Max,

I think that you are mischaracterizing yourself as a "reposter monkey". You are a much valued member of this community. You have not spent much time reading the many posts that I have made on methylprednisolone on CareCure. I am tired of repeatedly posting answers that you don't pay attention to. Your "rat-doctor" and other barbed comments about profits from the drug are unfair and unkind. Finally, the studies are not so complicated that people cannot understand them. In fact, it is very important that people with spinal cord injury try to understand these studies because many of them have received methylprednisolone and it is probably responsible for some of the recovery that many people have. I would suggest that you at least read the original papers and understand them before you start criticizing me or the studies.

1. Lack of evidence showing the MP is ineffective and unsafe. The doctors who have been criticizing methylprednisolone (MP) use have provided little evidence that the drug is ineffective and unsafe. It would seem reasonable to ask doctors who criticize a treatment that has been reported to be beneficial in three large double-blind, multicenter, randomized clinical trials to provide evidence that would contradict the evidence of efficacy and safety provided by the two NASCIS trials and the Japanese trial. The few studies that suggest a lack of effect or MP may have some complicating side effects are all single-center retrospective studies of relatively small numbers of patients. One double-blind study is a single-center study in France involved randomizing 100 patients to three treatments: methylprednisolone, nimodipine, and placebo. It did not segregate analysis of complete and incomplete spinal cord injury.

2. A priori hypotheses. Much of the criticism of the NASCIS are based on misunderstandings of the studies, i.e. that the studies engaged in post-hoc analyses of data. I want to point out that two NASCIS trials involved about nearly 500 patients each, underwent rigorous peer-review by NIH, and were published in the New England Journal of Medicine, the Journal of the American Medical Association, and the Journal of Neurosurgery. These trials were designed from the beginning to test the a priori hypotheses that timing of therapy and injury severity are important for treatment effects. The studies separately analyzed patients that were treated before and after the median time of treatment. The studies also stratified the patients into "complete" and "incomplete" before comparison. I will comment more on these two comparison strategies in greater detail below.

3. Treatment Timing. The trials were designed from the beginning to test the hypothesis that earlier treatment is better than later treatment. To test that hypothesis, both NASCIS 2 and 3 trials compared patients treated before and after the median time of treatment. The median time of treatment means half of the patients were treated before that time and half were treated after that time. In NASCIS 2, the median time of treatment was 8 hours and we found out that patients given MP before 8 hours showed significant beneficial effects while those given MP after 8 hours did not show a similar effect (and in fact may be worse than those who not treated). In NASCIS 3, the median time of treatment was 3 hours. Patients that were treated within 3 hours had the same outcome whether they were treated with a 24-hour course of MP, a 48-hour of MP, or a bolus dose of MP followed by a 48-hour course if tirilazad mesylate. However, patients that were treated with the 24-hour course of MP between 3-8 hours after injury recovered less than the 48-hour. The main conclusion of both NASCIS 2 and NASCIS 3 is that timing of treatment initiation is critical for the efficacy of the drug. We were the first study to show a therapeutic time window in spinal cord injury, a concept that is now widely accepted in clinical practice of all type of neuroprotective therapies.

4. Injury Severity. The NASCIS trials stratified the patients by injury severity, i.e. "complete" versus "incomplete". As most people at CareCure know, comparing recovery from complete and incomplete spinal cord injury is comparing two very different phenomena. The former typically recovers about 5% of function while the latter recovers 59% or more function. It is important to segregate the two groups because the recovery differences are so great. If there were 5% more patients with "incomplete" injuries in one treatment group, that group will have marked more recovery. The NASCIS trials were the first to segregate analyses of complete and incomplete patients. I believe that stratification by completeness of injury is necessary and trials that do not do so have a high risk of being imbalanced due to randomization. None of the clinical trials that are used to suggest that methylprednisolone segregated analyses of the patients by complete and incomplete spinal cord injury.

5. "Significance" of Treatment Effects. Many of the critics of the NASCIS trials said that neurological scores do not indicate "functional" recovery and pointed out that the trials did not assess "function". NASCIS 2 was carried out between 1985-1989. In the 1980's, there was no validated functional outcome measure. We developed and used a neurological scoring system. NASCIS 3 was carried out between 1992-1997 and we used the only validated functional recovery scale available at the time: the FIM score. NASCIS 2 showed statistically significant differences of neurological scores and NASCIS 3 showed statistically significant differences of both neurological and functional scores. The average recovery from methylprednisolone was also more than one segmental level. I challenge any clinician to look me in the face and tell me that they do not think that it is worthwhile for a person with spinal cord injury to recover one more segment.

6. Safety of Methylprednisolone. NASCIS 2 showed no significant difference of complications between MP-treated and placebo-treated patients. There was a statistically insignificant increase in wound infections rates from 3% to 7% (if I remember correctly). There was zero incidence of aseptic necrosis of joints. There was no difference in incidence of pneumonia, decubiti, urinary tract infection, and 36 other complications that were monitored. While there have been claims of complications from the standard 24-hour course of MP, none (I repeat, none) have been confirmed in randomized studies. NASCIS 3 suggested that there may be an increase in the number of severe pneumonias associated with the 48-hour course of MP. For that reason, we strongly recommended that the 24-hour course of MP be used if the treatment can be started within 3 hours of injury. The 48-hour course should be given only when treatment is started between 3-8 hours and clinician should carefully monitor the patients for pneumonia. By the way, the incidence of such pneumonia was not great, less than 7%. There was no difference in overall mortality or morbidity due to methylprednisolone treatment in both trials. I have conducted a detailed review of the literature for any complications associated with methylprednisolone and one study suggests precautions should be taken are in older patients (>60 years old).

I want to point that we have *never* claimed that MP is a miraculous therapy for SCI. We have emphasized over and over again that the effect of the drug is modest and that better therapies are needed. In fact, NASCIS 2 compared MP against naloxone, in our effort to find a better therapy. MP was better than naloxone. NASCIS 3 compared MP against tirilazad mesylate (TM) and MP was better than TM. That is why we continue to recommend MP. Nothing would please me more than another clinical trial showing a therapy that is better than MP. It is sad that this therapy that I started studying in 1979 is still the only therapy shown to be beneficial for acute spinal cord injury.

Regarding who is making a profit from MP, the drug was already of out patent by 1986 (the time when we started NASCIS 2) and NASCIS never received significant funding from Upjohn (the company that made methylprednisolone at that time). In New York through the 1990's, 10 grams of the drug costed about $100 (I don't know how much the cost is today). Pharmacia acquired Upjohn and Pfizer acquired Pharmacia. The drug is now made generically by many companies. I give lectures occasionally for Pfizer and donate all my honoraria to spinal cord injury research. Upjohn, Pharmacia, and Pfizer have all donated to significantly to the Neurotrauma Society which has held meetings with the funds. To my knowledge, I have never held stock in Upjohn, Pharmacia, or Pfizer (it is possible that I held mutual funds that included Pfizer but I did not knowingly hold stock in these companies or personally profited from MP in any way).

Finally, I want to point that that clinicians and people who attack MP are not doing spinal cord injury research any favors. I am hearing about more and more patients who are not receiving methylprednisolone for a variety of reasons. It is sad because MP is the only treatment that has been shown to improve function after spinal cord injury in humans. It is safe and cheap. It has been shown in hundreds of animal studies to have beneficial effects. It has been approved for use in multiple sclerosis and lupus erthymetosus. It was the drug that saved the lives of hundreds of people who got SARS in China. Millions of people have received methylprednisolone around the world for many conditions.

Wise.

Wise,

I'm just reposter monkey;)

Yes, I do sometime upleasant comments...

But I don't see your comments about articles, in my opinion damaging your reputation in scientific magasines...Where you can find equal opponents!

Do you really think I shoud get a degree in biology?..Just to conquer/oppose you?...I ain't marching anymore (Phil Okcs)

You are silly man;) if you think so...you got other bunch of peopla-to think way you do

Things about MP reapear somehow miraculously-sure I will stop commenting on them and about 4-Ap..Is this still a free website, or isn't it?

Ask yourself why practicing neurosurgereons are Questioning MP?

They seem to have nothing to gain?..Its well known fact -In US and Canada-that practicing Drs. are in cohuts:) with each other, no one will dare to testify in court agaist others malpractice...You know powerful Unions--So do those voices conspired again MP?...I bet more to come..

Continue rubbing shoulders with powerful ones???...one day it might or might not work for you..time will tell.esc versus adult!

With all my respect

I do post/repost everyting I find useful-to make people think

Thank you,

Max