Tuesday, 4 August 2015

NEDA-5: Neurofilaments

NEDA or 'No Evidence of Disease Activity' currently uses 4 parameters that are routinely collected in contemporary clinical trials:
  • Relapse activity
  • Disability progression
  • MRI activity
  • MRI atrophy
NEDA-4

NEDA has largely come into fruition with the introduction of highly active therapies, which for the first time allow us to achieve disease remission in MS. These therapies have set the benchmark, and as they grow in number so do our treatment expectations. And here starts the evolution in our definition of MS treatment strategies.

The Holy Grail of MS treatment strategy will always be in my books the achievement of biological remission, i.e. no further loss of axons or neurones throughout an MSer's life. We have in the past repeatedly blogged on neurofilaments as measures of axonal/neuronal integrity, disability progression and neuroprotection (insert 'neurofilaments' into the search this blog to find out more). As a strategy it is the future, but, I do not intend for it to remain simply a legend in the MS literature...

Therefore after extensive discussion, 'Barts MS' have decided to offer blood and CSF neurofilaments on the National Health Service on request via your doctor.

Sometimes you have to run before you can walk and that is how you push the boundaries of science, and in this case MS.


Mount Etna (located in Sicily) is Europe's tallest active volcano (the summit, on your right ~ 3300m high). Its eruptions cause widespread destruction and death, but is also vital for the nations survival.

Monitoring NEDA with Gd-enhanced MRI

How safe are frequent Gd-enhanced MRI scans? #MSBlog #MSResearch


"The following communication from the FDA is worrying, it suggest that people who undergo frequent gadolinium-enhanced MRI accumulate gadolinium (gD) in the brain long after the last administration. At present it unknown whether this is harmful or not. I have asked Professor David Miller to advise on this as it is very relevant to monitoring MS. We use Gd in clinical trials and routine clinical practice to monitor for active disease. In future we may have to limit ourselves to T2 scans only and count new and enlarging T2 lesions only. Please watch this space. Can I suggest you keep a log of how many Gd-enhanced scans you have had in case the information is needed for large-scale epidemiological studies to assess the effect of Gd on brain function."

FDA Drug Safety Communication: FDA evaluating the risk of brain deposits with repeated use of gadolinium-based contrast agents for magnetic resonance imaging (MRI)

Safety Announcement

The U.S. Food and Drug Administration (FDA) is investigating the risk of brain deposits following repeated use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI). MRIs help detect abnormalities of body organs, blood vessels, and other tissues. Recent publications in the medical literature have reported that deposits of GBCAs remain in the brains of some patients who undergo four or more contrast MRI scans, long after the last administration. It is unknown whether these gadolinium deposits are harmful or can lead to adverse health effects.

FDA, including its National Center for Toxicological Research (NCTR), will study this possible safety risk further. We are working with the research community and industry to understand the mechanism of gadolinium retention and to determine if there are any potential adverse health effects. Based on the need for additional information, at this time, we are not requiring manufacturers to make changes to the labels of GBCA products.

To reduce the potential for gadolinium accumulation, health care professionals should consider limiting GBCA use to clinical circumstances in which the additional information provided by the contrast is necessary. Health care professionals are also urged to reassess the necessity of repetitive GBCA MRIs in established treatment protocols.

Patients, parents, and caregivers should talk to their health care professionals if they have any questions about the use of GBCAs with MRIs. This issue affects only GBCAs; it does not apply to other types of scanning agents used for other imaging procedures, such as those that are iodine-based or radioisotopes.

After being administered, GBCAs are mostly eliminated from the body through the kidneys. However, trace amounts of gadolinium may stay in the body long-term. Recent studies conducted in people and animals have confirmed that gadolinium can remain in the brain, even in individuals with normal kidney function.1-21 Available information does not identify any adverse health effects.

We urge health care professionals, patients, and parents/caregivers to report possible side effects involving GBCAs to the FDA.

Neuros are Monkeys when it comes to assessing cognitive problems

Romero K, Shammi P, Feinstein A. Neurologists׳ accuracy in predicting cognitive impairment in multiple sclerosis. Mult Scler Relat Disord. 2015; 4:291-5.

Cognitive impairment affects approximately 40-70% of MS patients. As management of MS typically begins with, and is co-ordinated by neurologists, they are often the first to raise concerns about a patient׳s cognitive functioning. However, it is not known how accurate the neurological examination is in identifying cognitive impairment. To this end, we conducted a retrospective chart review of 97 MS patients referred by neurologists for neuropsychological assessment based on suspected cognitive impairment. Patients were classified as globally-impaired or intact according to failure on 2 or more of 11 cognitive indices comprising the MACFIMS, a recommended neuropsychological battery for MS. 


. Cognitively intact patients when compared to those who were impaired had higher levels of education and were less likely to have mood disturbances. These findings indicate the clinical interview and standard neurological examination are not sufficiently sensitive to detect cognitive impairment in MS, and suggest the need for a brief, accurate cognitive screen to complement routine clinical evaluation.
ProfG and NDG have not commented on this one, so they are clearly expecting some teasing about the ability of Neuros to spot cognitive problems. 

When you are a researcher you are told that MS is a just movement disorder and that it is a white matter disease. However, since attending "MS life" it has struck me how easy it was to spot cognitive/behavioural problems in some people with MS and made me think, how can MS just be considered to be a movement problem? Likewise a few minutes of looking properly and you can easily find grey matter problems, so how to neuros and pathologists get it so wrong. 

In this paper they look at who was sent for cognitive testing and neuros got it wrong about half the time. So maybe they need to listen rather than flip a coin to see who gets MACFIMS Minimal Assessment of Cognitive Function in MS. A 50:50% chance of getting it right or wrong is sometimes called a monkey score as this is what a monkey would get. 

Maybe it is time to have simple tests on computers or smart phones so we can remove the monkey from the neuro.

Would MS specialists get it wrong so
many times?