Vascular disease misdiagnosed as MS

[cheerleader]

Blocked cerebral bloodflow creates a disease that is mis-diagnosed as MS. Similar MRI presentation, similar symptoms. A vascular disease. hmmm.

A devastating vascular disorder of the brain called CADASIL, which strikes young adults and leads to early dementia, often is misdiagnosed as multiple sclerosis, Loyola University Health System researchers report. CADASIL occurs when thickening of blood vessel walls blocks blood flow in the brain. The early manifestation is migraine headaches, progressing to strokes and mini strokes, depression, apathy, motor disability and executive dysfunction (inability to plan and organize everyday activities.) The final symptom is dementia.

CADASIL is caused by mutations of a single gene called NOTCH 3. If an individual carries the mutated gene, he or she inevitably will develop the disease, and there's a 50 percent chance that each of the individual's children will inherit the mutation and the disease.

Researchers conducted an exhaustive series of genetic, physical and psychological tests and exams on 11 CADASIL patients. "We found a delay in the detection of this pathology and previous diagnostic errors in some patients and their relatives," researchers wrote. "Multiple sclerosis was the most frequent misdiagnosis."

The study is published in Revista de Neurologia (Journal of Neurology) in Spain.

The study was a subset of a larger study to determine whether the Alzheimer's disease drug donepezil (trade name, Aricept®) can help in CADASIL patients. This larger study found there generally was no benefit to the drug.

CADASIL stands for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. It was realistically portrayed by one of the main characters in the critically acclaimed 2004 movie "The Sea Inside."

"It is a terrible disease that runs in families, and unfortunately we as yet don't have effective treatments," said Dr. José Biller, senior author of the study and chairman of the Department of Neurology of Loyola University Chicago Stritch School of Medicine.

There are several reasons why CADASIL is misdiagnosed as MS. Both diseases tend to strike young adults. There are similarities in brain MRIs, and both diseases can cause focal neurologic signs and symptoms.

While there currently are no effective treatments, researchers are making significant progress in better understanding CADASIL, Biller said. "The field is exploding, and there is hope down the road that there will be new treatments for these patients," Biller said.

link

cheer

[ikulo]

But these aren't demyelinating lesions, are they?

I'm not sure where this fits into the CCSVI hypothesis...?

[frodo]

Well, reading their report maybe they could have said better that MS appears in CADASIL patients.

They did not prove that CADASIL lesions are not MS. In fact it is impossible to prove that without a pathological definition of MS, which does not exists, as far as I know.

[Asher]

hmmm what? An animal with 4 legs wagging their tail in not necessarily a dog, but Neurologists are trained to detect MS, so they detect MS. Zamboni is trained to detect blocked veins, so he sees blocked veins, especially in a sample that is not blind and not randomized.

[bluesky63]

CADASIL is frequently misdiagnosed as MS. In one of my support groups we had a woman whose husband ended up being redx'd as CADASIL so we talked a lot about this. The husband was only correctly diagnosed after persistent research by the family, because he had such cognitive trouble. The lesions can appear very similar. And the picture can be more or less aggressive, so absolutely this can be mistaken for MS, especially since many, many people who are given an MS diagnosis do NOT get an exhaustive diagnostic workup.

One of the biggest things I am always pointing is that up to 10 percent of people who have an MS diagnosis have been misdiagnosed. And that very few people get a truly thorough workup, or get followed to see if the original MS diagnosis still holds after a period of time.

It's not quite this simple, but a person presents to the doctor with a set of symptoms that could be anything from genetic disease to malabsorption to toxic poisoning to vascular disease to brain tumors toeven normal blips . . . the differential is VAST, and the lesions are more alike than you would think! MS is what's left when they can't find a different diagnosis. For some people, a persistent doctor will still find a different diagnosis years after the initial MS diagnosis.

Again, that's reductive, because there is a set of "classic" MS presentations, symptoms, and progression. But there are also plenty of misdiagnosed people, and plenty of amazing other potential diagnosis possibilities out there.

[jimmylegs]

squiffy posted this research too... interesting bluesky.. it would be interesting to see a list of significant differences between CADISIL and CCSVI.

i agree, typically there does not seem to be enough work done on the 'other plausible explanation' part of the msdx process!

[1eye]

Here, I've got an idea...

A randomized, blinded clinical trial with a sample size of, say, 100 neurologists. We ask patients with a known diagnosis of 'MS' and patients with a known diagnosis of CADASIL to participate. They are randomized, and each neurologist is asked to diagnose these patients. The neurologists are not told what the patients have. As far as they know, these are all legitimate, undiagnosed referrals.

Each doctor is told that for one month all new patients will potentially be part of a randomized trial and will potentially have a known disease that no-one but the database will know about.

The patients are not blinded to the facts of the trial, so their knowledge that this is a test, along with their acting ability and ability to keep a straight face are crucial. They can be put through practice runs to get them used to the idea, and they can be asked to do the same with several doctors, blinding them at least to which one is the real "physician under test".

Known sufferers of various diseases are used to further randomize the tests, and again nobody but the database knows who has what.

No results identifying any patients or doctors are made public. Only the statistics.

Anybody up for it?

[Doodles]

Dr. Zamboni's study of the safety and efficacy of balloon angioplasty for CCSVI was an open label study and there is nothing wrong with that. Pharmaceutical companies and other researchers normally start investigations with open label studies. The conclusion of Dr. Zamboni's open label study is appropriate: that a further randomized control study was needed. It really is not accurate to assume that the study Dr. Zamboni and his colleagues conducted is not valuable or scientific because it was an open label study, nor is it accurate to assume that all studies are immediately double-blinded, randomized clinical trials.

[ThisIsMA]

Zamboni is trained to detect blocked veins, so he sees blocked veins, especially in a sample that is not blind

...but Zamboni's group also found CCSVI in a blinded study of 16 pwMS and 8 healthy controls. In that study they found CCSVI using doppler ultrasound in 100% of the psMS and in 0% of the healthy controls. 100 percent accuracy! The likelihood that this would occur by chance is extremely small.

http://www.thisisms.com/ftopict-15806.html

Color doppler ultrasound could eventually become the fastest, most accurate and affordable way for doctors to diagnose MS. If a person presenting with MS symptoms isn't found to also have CCSVI through ultrasound testing, then it would be time to start looking for an alternate diagnosis!

[bluesky63]

Here's a recent thread that also brings up CADASIL, along with some other interesting abstracts and info about cerebral hypoperfusion. Curioser and curioser.

http://www.thisisms.com/ftopict-15671.html

[drsclafani]

Zamboni is trained to detect blocked veins, so he sees blocked veins, especially in a sample that is not blind

...but Zamboni's group also found CCSVI in a blinded study of 16 pwMS and 8 healthy controls. In that study they found CCSVI using doppler ultrasound in 100% of the psMS and in 0% of the healthy controls. 100 percent accuracy! The likelihood that this would occur by chance is extremely small.

http://www.thisisms.com/ftopict-15806.html

Color doppler ultrasound could eventually become the fastest, most accurate and affordable way for doctors to diagnose MS. If a person presenting with MS symptoms isn't found to also have CCSVI through ultrasound testing, then it would be time to start looking for an alternate diagnosis!

The definition of multiple sclerosis includes exclusion of other causes of demyelination

If a known cause of demyelinzation was excluded in error by missing or misinterpreting testing and MS was then diagnosed, it would be a false positive diagnosis for MS.

[cheerleader]

A differential diagnosis is the right of every pwMS---there are literally 100 other diseases that are supposed to be checked before an MS dx is made. Add CADISIL to the list....these are demyelinating lesions and a presentation which mirrors MS. I believe extracranial venous malformations must be added, as well.

In the 1980s, when APS was being established by Dr. Hughes, there was a pushback from neurology to include this blood disorder as a differential. Because MS isn't supposed to look like a vascular disease. And now it is on the officlal list.
http://www.hughes-syndrome.org/overview.htm

And now we add CADASIL---

Here are the differential diagnosis from Univerisity of Wisconsin, which include cerebrovascular disease, TIA, stroke, vasculitis and Hughes.
http://www.neurology.wisc.edu/publicati ... euro_2.pdf

cheer

[jimmylegs]

in my case during ddx they did not listen to me about history of b12 deficiency. it's a much longer story than this but, there was one old test on my file that had a clean read of b12 level without supplements. it didn't show up on my doc's graph because it was a text string 'less than 75', not a number the computer could plot. the rest is history :S

[ThisIsMA]

The definition of multiple sclerosis includes exclusion of other causes of demyelination

If a known cause of demyelinzation was excluded in error by missing or misinterpreting testing and MS was then diagnosed, it would be a false positive diagnosis for MS.

Interesting, but if it turns out that 100% of pwMS have CCSVI, then either they will have to conclude that no one has MS, or they will have to change their definition of MS to include CCSVI.

The current definition of MS is pretty goofy anyway. Since they don't know what the cause of MS is, how can they exclude "other causes"? Other causes besides what? Other causes besides no known cause?

[bluesky63]

Great article. I disagree about the psychiatric conclusion, since so many of the differentials include "psychiatric" issues as part of their presentation, but otherwise a fascinating read.

(Just a few obvious ones -- celiac disease can first present as depression, schizophrenia, and psychosis; MS itself directly causes depression and bipolar issues; porphyria is widely known for its psychiatric features; and many, many of the other differentials specifically mention dementia, etc. I mean, think about it -- how can you have a disease affecting your brain and NOT have some sort of effect on your psychological expression??)

I bet some of us are wondering about the MS dx right now.

I personally have never been confident in my own dx because I have so many "red flags" and have not had a typical course -- more aggressive, more disability, etc. Maybe I'll take this list to the doctor.