Thursday, 8 November 2018

Prediagnostic PML

PML is a major worry concerning treatment of MS

Can the PML lesion be picked up before the development 


Scarpazza C, Signori A, Prosperini L, Sormani MP, Cosottini M, Capra R, Gerevini S; Italian PML Group.Early diagnosis of progressive multifocal leucoencephalopathy: longitudinal lesion evolution.J Neurol Neurosurg Psychiatry. 2018 Nov 2. pii: jnnp-2018-319208.

OBJECTIVE: Early diagnosis of natalizumab-related progressive multifocal leucoencephalopathy (NTZ-PML) in multiple sclerosis has been deemed a major priority by the regulatory agencies but has yet to become a reality. The current paper aims to: (1) investigate whether patients with NTZ-PML pass through a prolonged presymptomatic phase with MRI abnormalities, (2) estimate the longitudinal PML lesion volume increase during the presymptomatic phase and (3) estimate the presymptomatic phase length and its impact on therapy duration as a risk stratification parameter.

METHODS:All Italian patients who developed NTZ-PML between 2009 and 2018 were included. The data of patients with available prediagnostic MRI were analysed (n=41). Detailed clinical and neuroradiological information was available for each participant.
RESULTS:(1) PML lesions were detectable in the presymptomatic phase in 32/41 (78%) patients; (ii) the lesion volume increased by 62.8 % for each month spent in the prediagnostic phase; (3) the prediagnostic phase length was 150.8±74.9 days; (4) PML MRI features were detectable before the 24th month of therapy in 31.7 % of patients in our cohort.
CONCLUSIONS: Considering the latency of PML clinical manifestation, the presymptomatic phase length supports the usefulness of MRI surveillance every 3-4  months. Early diagnosis could prompt a better outcome for patients due to the relationship between lesion volume and JC virus infection. The insight from this study might also have an impact on risk stratification algorithms, as therapy duration as a parameter of stratification appears to need reassessment.

So evidence of PML is present some time before disease becomes manifest, but can your radiographer spot it?.


  1. "The insight from this study might also have an impact on risk stratification algorithms, as therapy duration as a parameter of stratification appears to need reassessment."
    The duration is already taken into account in the stratification algorithm, what do the authors mean with their conclusion?

    "but can your radiographer spot it?"
    Is it difficult to spot it and are there many pml lesion misses?

    1. I don't know if there are misses?
      Maybe DrK can comment

    2. At the limits presentation this week, it suggests that subclinical PML can be seen months before disease strikes, the question being is the 2 years before switching too long?

  2. A comment by Prof. Gavin Giovannoni on this study would be interesting. The is detectable. Pml with RM? Thank you

    1. I suspect that this not happen as he MrsG are on a special anniversary trip


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