ClinicSpeak: MRI monitoring for PML is simply not good enough yet

Are you having regular MRI PML monitoring scans? #ClinicSpeak #MSBlog #MSResearch

“Earlier this week a colleague of mine was discussing the junior doctors’ industrial action and how we must support them; which I do. The discussion got down to how at the core of the new junior contract is simply the downward income spiral facing doctors. My colleague mentioned that this is part of a global trend. I couldn’t agree more, it is part of a global trend as more and more of our work becomes automated. Doctors are earning less because their general skills are simply not as good as we think they should be and technology is proving better at doing it than we are. This is part of the process of creative destruction, which is driven by technology. Yes, there are losers, the doctors, but there are also winners, and the winners tend to be society, in this case patients.”

“The study below shows how much we need a technological solution for MRI monitoring, be it for MS disease activity or the detection of early PML. The study compared how good neuroradiologists were at agreeing with each other about new the occurrence of new lesions on MRI and whether or not these lesions were due to MS or early PML. Although the investigators’ conclude on a positive note the inter- and intra-rater agreement rates are simply not good enough. Why am I being so critical? Because PML is a life threatening disease and any delay in making the diagnosis at an individual patient level could be the difference between life and death.”

“When we started PML surveillance, with 3-monthly MRI scanning, in MSers who were JCV-seropositive and at high-risk of PML, I had to scare our neuroradiologists about the task in hand. Essentially if they missed early PML it could mean the difference between life and death, or minimal or severe disability, for the patient concerned. Missing PML could potentially have legal implications for the neuroradiologist concerned. Most neuroradiologists are used to diagnostic scans that can take literally minutes to read and report. In comparison, monitoring scans, particularly those for PML monitoring, need a lot of time. You first have to call up the old scans and compare each slice fom the new scan with the older scan and you have to repeat the process across multiple sequences (different imaging parameters). As the first signs of PML can be very subtle you have to look at each section of brain very carefully. This is a laborious process and takes a long-time, which is why neuroradiologists don’t like reading MS activity and PML monitoring scans. Enter technology. We acquired new software from Siemens that automatically compares images with each other and colour codes any changes. This allows the neuroradiologist to zoom in immediately and focus on what has changed between the old and new scans and focus their attention on the changes. All of a sudden the reading of these monitoring scans has sped up by an order of magnitude. What would we do without technology?”

“I see a future, an era, when the software will be clever enough to read the scans without human input. The software will almost certainly be quicker and more accurate than the human eye. Will this put neuroradiologists out of a job? Unlikely, this will free up the neuroradiologist time to do new and more interesting things; to innovate and improve. The only way we can protect our jobs and earning capacity to is to add-value, to make things better. Believe me the way we practice medicine, and neurology, is ripe for creative destruction; the status quo is simply not an option.”

“If you are JCV-positive and are at high-risk of getting PML you should be undergoing frequent MRI scans to pick-up PML early or you should consider coming off natalizumab and switching to a safer DMT. In short you don’t want to get PML if you can avoid it.” 

Epub: Wattjes et al. Diagnostic performance of brain MRI in pharmacovigilance of natalizumab-treated MS patients. Mult Scler. 2015 Nov 12. pii: 1352458515615225. 

BACKGROUND: In natalizumab-treated multiple sclerosis (MS) patients, magnetic resonance imaging (MRI) is considered as a sensitive tool in detecting both MS disease activity and progressive multifocal leukoencephalopathy (PML).

OBJECTIVE: To investigate the performance of neuroradiologists using brain MRI in detecting new MS lesions and asymptomatic PML lesions and in differentiating between MS and PML lesions in natalizumab-treated MS patients. The secondary aim was to investigate interrater variability.

METHODS: In this retrospective diagnostic study, four blinded neuroradiologists assessed reference and follow-up brain MRI scans of 48 natalizumab-treated MS patients with new asymptomatic PML lesions (n = 21) or new MS lesions (n = 20) or no new lesions (n = 7). Sensitivity and specificity for detection of new lesions in general (MS and PML lesions), MS and PML lesion differentiation, and PML detection were determined. Interrater agreement was calculated.

RESULTS: Overall sensitivity and specificity for the detection of new lesions regardless of whether MS or PML lesions were 77.4% and 89.3%, respectively; for PML-MS lesion differentiation, 74.2% and 84.7%, respectively; and for asymptomatic PML lesion detection, 59.5% and 91.7%, respectively. Interrater agreement for the tested categories was fair to moderate.

CONCLUSION: The diagnostic performance of trained neuroradiologists using brain MRI in pharmacovigilance of natalizumab-treated MS patients is moderately good. Interrater agreement among trained readers is fair to moderate.

CoI: multiple

12 thoughts on “ClinicSpeak: MRI monitoring for PML is simply not good enough yet”

  1. VERY interesting. Have done some recent reading on quite a bit of this. MRI's have varied resolutions and avg. slice step is apparently 2mm. Thus due to resolution is it possible to miss activity between the stepping motors in slices. Radiologists may also simply miss activity (especially here in the USA at least) as they are pushed to examine so many daily.There is of course technology coming forth in respect to MRI comparison out of India and there is ICOMetrix which I have communicated a bit with also using image filtering and comparisons to detect activity.The problem here (and probably even more so where you are) is costing of regular scans. My fiance' (on Tecfidera) only scant weeks back had to get into a rather demanding personality format to get monthly blood work done. In fact, the attending Neuro did not want to do that until this blog was mentioned in conversation and the most recent case of PML. Basically told him that evidence suggests there is no early indicator of rapid lymphocyte drop until its apparently too late. Then he capitulated. Sorta.He said to be exact that HIS experience with the med is either "Steady" no drop, "Gradual" drop which normally "bounces back" and ONLY within the first 3 months might that rapid drop occur. So, he recommended for 3 months she get monthly bloodwork and after that go quarterly.We (she and I) said to each other after, lets see what happens in the 3 months and she is slated for a new baseline MRI since the Neuro said her prior MRI (back in Feb) showed her MS as "active" when she was in the MRI (no Gadolinium as she has allergic reaction to it). Said we need get a new baseline, then wait another 6 months to actually see if Tecfidera is working.Whats that game with the marble? The table where you need avoid the ball falling into the holes while you traverse the board from start to finish? Cant recall the name. This strategy from the neuro appears born in similar principle.Additionally, there is new technology in development that essentially is a helmet a person can wear that not only can perform high resolution scan but also deep scan of the brain. Article is on our web as well. Just hit the site and search "MRI" should come up.

  2. I have PPMS. I've had it since my twenties. My walking is badly effected.My NHS neurologist has ceased sending me appointments. The reasons for his apathy is two pronged: firstly, there's little he can offer me, secondly, my attitude was always to ask what he's doing for me and questioning his vision for PPMS care. I guess that he felt undermined, but that's down to his insecurity.Neurology in MS care in the UK has become about concentrating on low lying fruit, looking after patients you can do something for and de-prioritsing those you can't. It is throughly shameful.I am glad that doctors are getting hit by government and devalued. They are largely useless and the public has little sympathy for their plight, especially when they are hardly poor and struggling. I wish them the worst.

    1. I've just participated in a research study by a doctor, whose aim is to make things better for people that have SPMS. Another side of MS that there isn't much that can be done to help us. It's the fault of junior doctors, there isn't a cure. What do you want from your clinician?

  3. Getting MRI's was bane of my life even after 40+ infusions of Tysabri. Last MRI (with contrast dye) in Oct. '13, before Tysabri stopped in Aug. '14 and when asked to see last MRI was refused, told not "worth it", didn't show anything and I'd 'probably progressed to SPMS'. When I asked how you can tell I was told 'clinical observation' / in wheelchair for appointment. Really knocked confidence & depressed for months. OKish now & very much reduced medication, but don't miss continually having to press for annual MRI & Stratify test results – often 18 months apart!

    1. The second neurologist (junior doctor) I ever saw I asked him if I could see my neck MRI scan. We were already looking at a scan of part of my brain. He turned to me and said "it's just a snap shot in time". So he didn't show it to me which I find strange, seeing I had paralysis in my arms (transverse myelitis) when I saw him. I went on to have a second MRI seven months later and I have a full TM lesion in my C spine.

  4. You do realise Prof G is trying to stir-up yet another debate! This time he is taking on the whole medical profession. His enthusiasm for controversy knows no limits.

    1. I guess you're right, though it didn't stop Prof G from banning Dr dre for his controversial comments,

    2. Get your facts right, no one has banned Dre and as to controversial comments not sure what we objected too in his comments either. It's up to him.

    3. Re: "You do realise Prof G is trying to stir-up yet another debate!"I am not sure what you are referring to. But creative destruction is well worn term to describe the economic impact of innovation. To date doctors have been slow adopters and have generally resisted change to the way we practice. All I am saying this has to change; we have no new money to expand and develop our services. We therefore are going to have to innovate and use technology. Using software to help neuroradiologists is only one example that will improve the service we provide MSers. I am not sure this is controversial.

    4. Howdy pilgrims. Tis I, Dr. Dre.Fret ye not, there is no ban, merely a misunderstanding. MouseDoc, in his lame way, kind of owned up to his mistake of not publishing a comment I issued to some MSer's request. MouseDoc stated he was on an errand to Guernsey or Ireland or someplace and misplaced my comment in the spam folder or something. Pathetic, I know, but MouseDoc is only human after all.So it's water under the bridge. I wanted an explanation and we got one. Hooray!Us doctors are an arrogant bunch and never like to say sorry. So from one doctor to another, I forgive you, MouseDoc.Now let's all have a coke and a smile and forget about it all.

    5. I'm good. I dont wish anyone ill will.Unfortunately a characteristic of years of involvement in political arena's is that at times my words can slice like a Star Wars light sabre. I try control it but sometimes its like awakening to an erection, "There it is, now what?"I'll go for the coffee and donut.I live in the USA, Coke + Smiles + Group Hugs here can result in birth defects or stronger NRA rights.

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