Methylprednisolone soon to be replaced as treatment of choice for Acutes???

[bigbob]

Originally Posted by Wise Young

NASCIS 2 was carried out between 1985 and 1989,

20 years later and this is where we are?

And, we are still told a cure will be here in 5 years

And, for some time a definition of that cure was that for all practical purposes no one would know that you were previously paralyzed?

[Monique]

Originally Posted by Wise Young

• NASCIS 2 randomized approximately 500 patients to placebo vs. MP (30 mg/kg bolus plus 5.4 mg/kg/hour for 23 hours) vs. naloxone (5.4 mg/kg x 3 mg/kg/hour x 23 hours).

Why naloxone? I only know that it is an opiate receptor competitve antagonist, and recently learned that it is given to unconscious patients in the ER because of the possibilty of a drug (opiate) overdose.

Originally Posted by Wise Young

In summary, the NASCIS trials showed that early with high-dose MP for 24 hours modestly improved neurological function of patients with spinal cord injury, a 48-hour course of MP is more effective than 24-hour course of MP, when treatment was started more than 3 hours after injury.

If a 48-hour course is more effective if started 3 hours after injury, how come only a 24-hour course is given even in that case (or is it?)?

[Wise Young]

Originally Posted by Monique

Why naloxone? I only know that it is an opiate receptor competitve antagonist, and recently learned that it is given to unconscious patients in the ER because of the possibilty of a drug (opiate) overdose.

If a 48-hour course is more effective if started 3 hours after injury, how come only a 24-hour course is given even in that case (or is it?)?

Monique,

One of my earliest papers at NYU was a study reporting the naloxone improves blood flow, somatosensory evoked potentials, and locomotor recovery in cats after spinal cord injury. NASCIS 2 showed that naloxone produced an intermediate level of recovery between methylprednisolone and naloxone. Although the naloxone effect was not statistically significantly different from placebo using the conservative first level analysis, subsequent post-hoc analyses indicated that it was different although not as good as the 24-hour course of methylprednisolone in humans. Therefore, we recommended methylprednisolone.

NASCIS 3 showed that when patients are started on methylprednisolone more than 3 hours after injury, the 48-hour course of the treatment is significantly better than the 24-hour course. However, although there was no overall increase in the incidence of pneumonia, there was a small increase in the incidence of severe pneumonias in patients receiving the 48-hour course of the drug. There was no difference the 24-hour or 48-hour courses of methylprednisolone when it was started within 3 hours after injury. Therefore, we recommended that patients receive the 48-hour course if the treatment is started between 3-8 hours after injury.

NASCIS 2 had shown that starting methylprednisolone more than 8 hours after injury was not only ineffective but may have worse neurological outcomes. We therefore recommended that the treatment not be given if it cannot be started within 8 hours after injury.

Wise.

[Sue Pendleton]

Originally Posted by Faye

AND after Jason had been on valium for four months in the PICU and in rehab, I found out that rats who had been administered valium never recovered motor function......( valium is routinely used as palliative care to make "patients more manageable").
Desperately and promptly I weaned Jason off the valium.

We tried to salvage as many cells as possible that first year post LIS ( apoptosis can continue that long after injury), by doing hyperbaric oxygen treatments and going to the primavera clinic on the island of Cypress.

I wonder if we read the same study, Faye. I didn't even want a PC in my house for 4 years after my spinal infarct. I thought it would make my world even smaller. Then I found I could read the entire medical library in Hong Kong from our den! Which, I think (it has been awhile), is where I found a study that said giving ANY sedative to someone suffering a stroke of the brain reduces their return of function significantly. While my stroke was at C4 and well below the brain I was sedated to keep the respirator in. I have chipped teeth from trying to gnaw that thing off. The Germans believe in minimal meds but they really didn't have much choice.

I do credit getting off that vent within the 10 day window they set for preforming tracheostomies on the MP I got. And a nurse who stayed well past her shift for a week to work just on me to get me awake and breathing. It sucked waking up when you're in such a wonderful somewhere in between world but I thank her for her dedication everytime I breathe.

I do take valium now for spasms because I can use it as needed. Well, and none of the other meds work on me.

How did the hyperbaric oxygen work? I had a PT that wanted me to try it about 6 years post. Life got in the way or I would have.
(Spelling, what else?)

[Wise Young]

I moved a post by BigBob concerning hyperbaric oxygenation at Penn to the appropriate thread. Wise.

[antiquity]

As Lindox pointed out, MP is a treatment modality, it has never been promoted as a cure.

My injury occured before MP was available and I didn't recover. Why assume that Jason's failure to recover was due to the MP when people not given MP fail to recover?

I would think the reasons have more to do with the dilantin and valium Jason received. I was put on adult doses of tofranil at age 8 to 'train' my bladder for months after my injury. Tofranil also inhibits cns recovery and regeneration. It may be why I was one of the few juvenile onset SCI's who remained complete.

Dr. Young has stated many times that he hoped another treatment for acute SCI would have been developed by now.

20 years later and this is where we are?

Yes Bob, nothing since then, sad huh? Where have all of the other researchers been? Hope you badger them as much as you do Wise, but wait, they don't make themselves available on public message boards like Wise does for that very reason.

Why did you take issue with Wise because MP ISN'T the standard treatment protocol for acute sci outside of the US in one thread then take issue with him because it is standard protocol at trauma centers here?

[Faye]

Originally Posted by SuePendleton

where I found a study that said giving ANY sedative to someone suffering a stroke of the brain reduces their return of function significantly. While my stroke was at C4 and well below the brain I was sedated to keep the respirator in. I have chipped teeth from trying to gnaw that thing off. The Germans believe in minimal meds but they really didn't have much choice.

Exactly: ANY sedative reduces neuronregeneration. To prep Jason for transportation to a renowned children's hospital ( when his neurons were still salvageable) and he was "combative" from intense pain and excessive firing of neurons, he was given adevan, which I was told would help him "forget" this traumatic event.

We need to educate people treating those with neurological problems NOT to give them sedatives. Better suffer intense pain for several hours than suffer reduced neurological recovery.

As far as the hyperbaric oxygen treatments are concerned. I wish they had them available in every emergency room, because immediate treatment would have prvented the neurnonal damage from the ischemia caused by Jason's bloodclot.
However, nobody told us about HBO until 9 months laterand it had absolutely no functional effect on Jason except for improvements noted on a comparison of before and after SPECT study. He underwent 60 treatments.

Originally Posted by seneca

As Lindox pointed out, MP is a treatment modality, it has never been promoted as a cure.

My injury occured before MP was available and I didn't recover. Why assume that Jason's failure to recover was due to the MP when people not given MP fail to recover?

I would think the reasons have more to do with the dilantin and valium Jason received. I was put on adult doses of tofranil at age 8 to 'train' my bladder for months after my injury. Tofranil also inhibits cns recovery and regeneration. It may be why I was one of the few juvenile onset SCI's who remained complete.

Seneca, I agree that the dilantin and the valium are mostly responsible for very limited recovery. As you know children are told they will recover better than adults and we have simply not experienced that.

On MP I just feel that cases that are primarily caused by an inflamatory condition such as ADEM or TM probably do better.

[Wise Young]

Methylprednisolone will reduce sprouting and axonal growth if it is given for longer than 24-48 hours. It is neuroprotective but when it is given for longer than 48 hours, it may reduce recovery. That is why we have been so careful in our clinical trials to give it only for a limited period of time. It is well known that methylprednisolone, in addition to shutting down pro-inflammatory cytokine gene expression, will shut down neurotrophin expression. The first NASCIS trial gave methylprednisolone for 10 days. I don't know how long Jason received methylprednisolone, if any.

Wise.

[Faye]

Originally Posted by Wise Young

Methylprednisolone will reduce sprouting and axonal growth if it is given for longer than 24-48 hours. It is neuroprotective but when it is given for longer than 48 hours, it may reduce recovery. That is why we have been so careful in our clinical trials to give it only for a limited period of time. It is well known that methylprednisolone, in addition to shutting down pro-inflammatory cytokine gene expression, will shut down neurotrophin expression. The first NASCIS trial gave methylprednisolone for 10 days. I don't know how long Jason received methylprednisolone, if any.

Wise.

Good question. Jason had two 24 hour courses of MP, a month apart. It seems like they followed the protocol of starting with a bolus....

Regarding the first 24 hour course, I must admit that the before and after MRI's show a reduction in the size of the lesion in the pons.

This in itself sounds good, although I caution people that the size of the lesion doesn't necessarily correlate with better or worse function. In Jason's case there was no notable change in function ie he could still only move his eyes and had no movement in any other part of the body. ( the reduction in lesion size was nevertheless cause for optimism)

For example even a better SPECT image showing increased perfusion/activity in the brain after HBO, may not necessarily correspond with better function either.

In Jason's case I have been more concerned in retrospect with the continued administration of prednison while in rehab( after the MP course which was administered in PICU) as with Jerry Lee Lewis, who like Jason developed "moon face". http://news.bbc.co.uk/1/hi/entertain...iz/3279553.stm

Maybe Dr. Young can explain how MP and prednisone differ.

But I am very concerned that the continued administration of sedatives and prednisone in combination caused a reduction in neuro-regeneration in Jason. Nothing I can do about it now, just hope we can try to maximize potential improvements in others by avoiding the routine administration of these agents that actually reduce neuro-regeneration.

[Wise Young]

Originally Posted by Faye

Good question. Jason had two 24 hour courses of MP, a month apart. It seems like they followed the protocol of starting with a bolus....

Regarding the first 24 hour course, I must admit that the before and after MRI's show a reduction in the size of the lesion in the pons.

This in itself sounds good, although I caution people that the size of the lesion doesn't necessarily correlate with better or worse function. In Jason's case there was no notable change in function ie he could still only move his eyes and had no movement in any other part of the body. ( the reduction in lesion size was nevertheless cause for optimism)

For example even a better SPECT image showing increased perfusion/activity in the brain after HBO, may not necessarily correspond with better function either.

In Jason's case I have been more concerned in retrospect with the continued administration of prednison while in rehab( after the MP course which was administered in PICU) as with Jerry Lee Lewis, who like Jason developed "moon face". http://news.bbc.co.uk/1/hi/entertain...iz/3279553.stm

Maybe Dr. Young can explain how MP and prednisone differ.

But I am very concerned that the continued administration of sedatives and prednisone in combination caused a reduction in neuro-regeneration in Jason. Nothing I can do about it now, just hope we can try to maximize potential improvements in others by reduction the routine administration of these agents that actually reduce neuro-regeneration.

Methylprednisolone is given as an intravenous solution called Solumedrol or methylprednisolone sodium succinate (MPSS). As I understand it, MPSS needs to pass through the liver so that the succinate can be broken off before it starts to act as a glucocorticoid.

Prednisone is an glucocorticoid that can be given orally. It is usually given when people take longer term oral glucocorticoids. Did Jason receive prednisone for a period of time after the methylprednisolone? It sounds like it, given your description of his "moon-face". If so, I suspect that this may have inhibited his recovery.

Until there is more evidence, I don't think that speculation about sedatives slowing or stopping neurological recovery is well-justified. In contrast to the known suppressive effects of long-term glucocorticoids on axonal growth, the evidence that anti-spasticity drugs, anti-epileptics, and tranquilizers affect recovery is still very limited and not yet convincing. Also, it is important not to equate these very different clases of drugs. For example, dilantin and benzodiazepines are quite different from each other. Dilantin is an anti-epileptic while benzadiazepines bind to gaba receptors.



Wise.