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Joined: May 26, 2004 Posts: 1356 Location: London, ON, Canada
Posted: Sun Jul 13, 2008 8:54 am Post subject: Autopsy
Last September, after my wife Marg passed away, I had asked the hospital to conduct an autopsy. She had MS for 36 years and I wanted to learn how extensive the disease had progressed and what caused her death. It took 8 months before all the information was available and I discussed these findings with Marg's neurologist and also got an opinion from another person involved in MS research.
As for the cause of death....sepsis which was part of several digestive tract problems which ended up causing Pancreatitis and severe infection in the abdomen.
But the neurology results were very interesting. The only lesions in Marg's brain were very old, likely from her original attack in 1971. During a drug trial in 1997, several MRI's showed these old lesions without any further evidence of MS progression.
The spinal cord, however, told a VERY different story. Several lesions were seen in the autopsy along with a flattening and thinning of a large area of the spinal cord itself. The neurologist told me that this kind of damage was often seen in MS patients who have had the disease for a long time. He sent me an abstract of a study they had done on this very problem. The study confirmed this kind of possible problem but despite all the latest info about MS, nobody had an explanation as to why this happened to the spinal cord!! Sound familiar when trying to understand this disease?
I find it perplexing that for all the years Marg had MS, the docs never did an MRI of her spine to see if her progression of the disease was a result of what was going on in this area. Even during the drug trial, this was not done. From what I have read as well, I can't recall MS patients in drug trials having MRI's of their spine being done.
Doesn't seem to make sense that the spine area seems to be ignored with all the concentration of resources being done on brain MRIs. I certainly would like to see some comments about this from the many readers on this forum.
Joined: Sep 12, 2006 Posts: 865 Location: Dayton, Ohio USA
Posted: Sun Jul 13, 2008 9:41 am Post subject:
That does seem kind of perplexing. If you look at things like Devic's, there are places on your spinal cord where you definitely DO NOT want lesions. I've had a few MRI's of my spine, but they weren't part of the trial I'm in. Interesting. _________________ "When you're in jail, a good friend will be trying to bail you out. A best friend will be in the cell next to you saying, 'Damn, that was fun.'"
Harry, I'm glad you got some info about the autopsy. I guess my first symptoms must have screamed "spinal cord!" to the neuros because that was the first MRI I had, before my diagnosis. I wonder why Marg's neuros never order an MRI of her spinal cord. I sometimes feel like doctors in Canada are too conscious of being gate-keepers for the medical system and only want to use resources like MRIs when it is considered absolutely essential.
I had a brain and spinal cord MRI as part of my dx - lesions in both areas. I think I have had around a dozen MRIs as part of my Campath trial - but only of the head (brain). I think the reason for this is cost - in the UK MRI scanners are heavily booked and therefore for trials its easier and cheaper for just a head MRI.
Joined: Sep 11, 2007 Posts: 667 Location: southern California
Posted: Sun Jul 13, 2008 11:08 am Post subject:
Dear Harry-
Thank you from all of us for sharing Marg's autopsy results. My husband Jeff's first MRI included brain and cervical spine. I wondered why the complete spine wasn't included, and asked his neuro. She cited the cost, and that Jeff's MS progression would be evident from his brain. Obviously, as Marg has proven, that's not always true. This would also explain why folks who have had MS for a long time, without enhancing lesions on the brain, might well be deteriorating, undetected, along the spinal column.
from one spouse to another, many thanks-
AC _________________ Husband diagnosed RRMS March 2007
pursuing endothelial healing
Copaxone, Swank, supplements, laughter
Joined: Sep 11, 2007 Posts: 667 Location: southern California
Posted: Sun Jul 13, 2008 11:34 am Post subject:
Here's some more info on spinal MRI's, explains why it's not performed more regularly...
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1032291
Abstract-
The clinical and pathological manifestations of multiple sclerosis are due to areas of demyelination which occur throughout the white matter of the central nervous system. MRI of the brain frequently shows abnormalities in the hemispheric subcortical white matter; these are demonstrable in the majority of patients and support the clinical diagnosis of multiple sclerosis. Our studies have shown that while MRI identifies such cerebral lesions in nearly all clinically definite multiple sclerosis patients with illness of duration greater than 10 years, these areas of abnormal T2 signal are present less often in the brains of patients studied within 3 years of disease onset. However, symptoms referable to the long tracts of the spinal cord are prominent in many of these patients. Imaging of the spinal cord has presented technical problems because of the small size of the cord, patient body, heart and respiratory movements, and limitations of surface coil technology. The spinal cord of 77 patients with multiple sclerosis have been imaged, revealing three types of abnormalities: (1) approximately half the cords show regions of abnormal T2 weighted signal; (2) during acute exacerbation, spinal cord enlargement (swelling) may be observed; (3) spinal cord atrophy (narrowing) is found particularly in patients with disease of longer duration and greater disability. Unlike the presence of brain lesions, the existence of spinal cord lesions of high T2 signal is not associated with increasing duration of disease but is correlated with disability status. Of patients with such lesions about one fifth did not exhibit brain lesions discernible by MRI. _________________ Husband diagnosed RRMS March 2007
pursuing endothelial healing
Copaxone, Swank, supplements, laughter
Could it be that the holes in CNS were easy to repair for being the central plasticity better than the one of the spinal cord and that explain that sometimes disappear in the brain and not in the spinal cord and that was what provokes the real disability ?
Marg's case would certainly relate to me because I do not show brain lesions although I am a 6.5 on the EDSS scale.
I had a full spinal MRI about 12 years ago whe I was probably a 5 or so on the scale which also showed nothing. Maybe I would show lesions now in the spine, but there is nothing that could be done about it if there were some, so I would not willingly have another MRI done.
I really would like to see if they checked out her gray matter for damage since that is what some researchers believe is the area that is so damaging to SPMS and progressive types rather than the lesions and inflammation.
Joined: Nov 08, 2004 Posts: 144 Location: Colorado
Posted: Sun Jul 13, 2008 1:45 pm Post subject:
Thank you Harry for following-up with the autopsy report. I personally know how hard it is to decide to get an autopsy and then read the report. My husband was being treated for cancer and died suddenly. I needed to know what happened because his death was so unexpected, so I requested an autopsy. Report said he was cancer free and that he died of a ruptured abdominal aneurysm ---answers which I was not expecting but at least I knew what happened. I would imagine Marg's report has helped you also.
I had a brain and a cervical spine MRI when first diagnosed. The neuro continues to schedule a brain MRI every year and a cervical spine every other year. Both MRI's have remained unchanged since the first. I have three lesions in the cervical cord which have never shown enhancement; I have four lesions in the brain which have never shown enhancement; and I have a capillary telangiectasia (brain stem vascular malformation) in the pons area which does show enhancement. This is unrelated to MS. My EDSS is 3, I am 65 years of age, no CRAB drugs, started LDN about three months ago, play golf twice a week, limp on my left side, use a Walk-Aide and generally do just about anything I want. Oh, I think I have had MS for about 35 years. A crazy, crazy disease!!! It is so different for everyone.
Take care of yourself Harry - you spent many years and hours lovingly caring for Marg - it is your time to enjoy.
Could it be that the holes in CNS were easy to repair for being the central plasticity better than the one of the spinal cord and that explain that sometimes disappear in the brain and not in the spinal cord and that was what provokes the real disability ?
This is my guess as well. Fits well with the aggressive nature of PPMS and its tendency to be on the spinal cord. On a more positive note, while nervous system repair is still a ways off I feel like we'll see spinal repair before brain.
Thank you Harry for posting the results and for sharing the information with us.
I have had one cervical MRI but since then only brain. Whenever I questioned my neurologist about doing another cervical she said she only needed the brain. Even though I have a couple of lesions on my spine. When I went to Vanderbilt the first time the neurologist (MS specialist) asked why I didn't have an updated cervical. I told him it was never ordered. I just returned from my follow-up appointment with him in June and he said that when I return in January he wants me to have had BOTH a brain and cervical MRI so he could see what was happening. So I took away from that that he felt the cervical was important. After reading your post about your wife I am glad that he is insisting on it.
Posted: Sun Jul 13, 2008 5:57 pm Post subject: Spinal and Cervical Cord Atrophy in MS
Harry
Thanks so much for letting us know the results of Marge’s autopsy. I hope that if you’ve given permission, that some neurologist will find a way to use it to move MS research forward in this area. I think it’s sorely needed.
Personally I don’t think the finding of a thinning and flattened spinal cord should be all that surprising per what the neuro shared with you, but why it doesn’t get more attention is puzzling since there is research in this area. It could be as mentioned that it’s simply difficult to measure and there aren’t standardized methods yet.
There seems to be little doubt that spinal cord atrophy is linked to disability. And, just like brain atrophy, the loss of axons, neurons and the neurodegeneration doesn't seem to be limited to “lesions“. The current focus of research in this area seems to be on upper cervical cord atrophy.
Previous studies have shown that upper cervical cord atrophy (UCCA) occurs in multiple sclerosis (MS), particularly in those disabled and with primary or secondary progressive disease.
Longitudinal analysis showed a significant decrease in UCCA in patients both within the patient cohort (p < 0.001) and in comparison with controls (p = 0.001). There was a significant increase in EDSS (p = 0.008) but no significant change in MSFC. The rate of UCCA loss did not correlate with clinical change or with change in brain volume.
CONCLUSIONS: In summary, serial UCCA measurement detects the development of spinal cord atrophy in clinically early RR MS.
In this study, MRS was used to investigate the degree of neuronal damage in the cervical spinal cord in MS.
Concentration of the neuronal metabolite N-acetyl-aspartate ([NAA]) was reduced in the spinal cord in MS patients relative to controls (reduced by 32%, P < 0.05), indicating significant neuronal damage.
Additionally, the spinal cord was significantly atrophied in MS patients (15%, P < 0.001). No significant reduction in brain [NAA] was seen in the MS group.
MRS demonstrated cellular damage within the cord over and above the tissue atrophy seen by MRI. Combining MRI and MRS may therefore give a more complete picture of neurodegeneration in the spinal cord.
The following research was published in 2000, so the subject isn’t new.
Axonal loss in MS lesions ranged from 45 to 84% and averaged 68%. NAA levels were significantly reduced (>50%) in cross sections of spinal cords containing MS lesions. Reduced NAA correlated with reduced axonal numbers within lesion areas.
In addition, NAA levels per axonal volume were significantly reduced in demyelinated axons (42%) and in myelinated axons in normal-appearing white matter (30%).
The data support axonal loss as a major cause of irreversible neurological disability in paralyzed MS patients and indicate that reduced NAA as measured by magnetic resonance spectroscopy can reflect axonal loss and reduced NAA levels in demyelinated and myelinated axons.
And, of course several years ago Finn informed us of this research:
Imaging studies in multiple sclerosis have shown that spinal cord atrophy correlates with clinical disability
The multiple sclerosis cords were found to be significantly smaller than the controls.
The duration of the disease played the most important role in determining cord atrophy.
The degree of atrophy varied in different parts of the cord.
Individual lesions played a minor role in local atrophy.
Our findings suggest that axonal degeneration, possibly caused by the cumulative number of lesions in the brain and cord, or an alternative atrophic process, is responsible for spinal cord atrophy in multiple sclerosis, rather than tissue loss within individual lesions.
Still lots to learn about this disease and I’m so grateful you’ve shared the results of Marge’s autopsy. It’s very valuable information.
Joined: May 26, 2004 Posts: 1356 Location: London, ON, Canada
Posted: Mon Jul 14, 2008 7:13 am Post subject:
Quote:
Thanks to everyone else for the interesting input to read.
Bob
I'll certainly second that comment, Bob! I thought that there would be a number of interesting comments on my post and I also thank you all for the kind notes as well.
I'm going to add another observation....over the past 20 years or so, the trials for the current approved MS drugs have hung their results on the number of brain lesions that show up on the patients' MRIs. But if the lesions and consequent damage is happening in the spinal cord, would not the trial results be very wrong in some of these patients? Just a thought.
And Sharon...I have already taken your advice of looking after myself after all these years of care giving. I have recently met a wonderful lady friend and am starting to enjoy life again.
Harry
Last edited by HarryZ on Mon Jul 14, 2008 1:23 pm; edited 1 time in total
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