Friday, 26 August 2016

ClinicSpeak & ResearchSpeak: distinguishing PML from MS

Does your neuroradiologist know how to distinguish between PML and MS? #ClinicSpeak #ResearchSpeak #MSBlog

"If you you are JCV-seropositive and are on natalizumab (Tysabri) you are at risk of developing PML. Depending on your how long you have been on natalizumab and your anti-JCV antibody index you may be having frequent MRI scans to monitor for early asymptomatic PML. The rationale is that if you pick-up PML very early before you have any symptoms and stop natalizumab you do much better in terms of outcome. The study below identifies characteristics of early PML lesions that distinguish then from new MS lesions. The presence of punctate T2 lesions, cortical grey matter involvement, white matter lesions next to the cortex, ill-defined and mixed lesion borders towards both grey and white matter, lesions larger than >3 cm in size and interestingly contrast enhancement were all associated with PML compared to new MS lesions. In contrast, well-defined focal lesions and localisation next to the ventricles were associated with new MS lesions. This findings are not trivial and I would encourage you to make sure that the neuroradiologist(s) who is/are reading your PML-surveillance scans have read this paper."

"What this paper does not describe is how rarely new T2 lesions develop on natalizumab treatment after the first 12 months. Another point worth mentioning is that now that we have so many treatment options if you are at high-risk of developing PML you really should consider transitioning onto another DMT. I know natalizumab is very effective drug, but we really should be trying to prevent any further cases of PML."


Wijburg et al. MRI criteria differentiating asymptomatic PML from new MS lesions during natalizumab pharmacovigilance. J Neurol Neurosurg Psychiatry. 2016 Aug 16. pii: jnnp-2016-313772. doi: 10.1136/jnnp-2016-313772. [Epub]

OBJECTIVE: Differentiation between progressive multifocal leukoencephalopathy (PML) and new multiple sclerosis (MS) lesions on brain MRI during natalizumab pharmacovigilance in the absence of clinical signs and symptoms is challenging but is of substantial clinical relevance. We aim to define MRI characteristics that can aid in this differentiation.
METHODS: Reference and follow-up brain MRIs of natalizumab-treated patients with MS with asymptomatic PML (n=21), or asymptomatic new MS lesions (n=20) were evaluated with respect to characteristics of newly detected lesions by four blinded raters. We tested the association with PML for each characteristic and constructed a multivariable prediction model which we analysed using a receiver operating characteristic (ROC) curve.

RESULTS: Presence of punctate T2 lesions, cortical grey matter involvement, juxtacortical white matter involvement, ill-defined and mixed lesion borders towards both grey and white matter, lesion size of >3 cm, and contrast enhancement were all associated with PML. Focal lesion appearance and periventricular localisation were associated with new MS lesions. In the multivariable model, punctate T2 lesions and cortical grey matter involvement predict for PML, while focal lesion appearance and periventricular localisation predict for new MS lesions (area under the curve: 0.988, 95% CI 0.977 to 1.0, sensitivity: 100%, specificity: 80.6%).

INTERPRETATION: The MRI characteristics of asymptomatic natalizumab-associated PML lesions proved to differ from new MS lesions. This led to a prediction model with a high discriminating power. Careful assessment of the presence of punctate T2 lesions, cortical grey matter involvement, focal lesion appearance and periventricular localisation allows for an early diagnosis of PML.

3 comments:

  1. OK so which threpy is as effective in percentage terms as tysabi is? Because I haven't been informed of a better proven therapy long term.

    ReplyDelete
    Replies
    1. Lemtrada seems to have similar efficacy.

      Delete
  2. We are planning for the off-natalizumab transition. I know this wonderful blog addresses that occasionally but can't seem to find it. Can anyone point me in the right direction? Thanks!

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