If you have the Lumper’s you get the Splitters too. Can imaging spot the progressors

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Diagnosis of Progressive Multiple Sclerosis From the Imaging PerspectiveA ReviewFilippi et al. JAMA Neurol 2020. doi:10.1001/jamaneurol.2020.4689

Importance  Although magnetic resonance imaging (MRI) is useful for monitoring disease dissemination in space and over time and excluding multiple sclerosis (MS) mimics, there has been less application of MRI to progressive MS, including diagnosing primary progressive (PP) MS and identifying patients with relapsing-remitting (RR) MS who are at risk of developing secondary progressive (SP) MS. This review addresses clinical application of MRI for both diagnosis and prognosis of progressive MS.

Observations  Although nonspecific, some spinal cord imaging features (diffuse abnormalities and lesions involving gray matter [GM] and ≥2 white matter columns) are typical of PPMS. In patients with PPMS and those with relapse-onset MS, location of lesions in critical central nervous system regions (spinal cord, infratentorial regions, and GM) and MRI-detected high inflammatory activity in the first years after diagnosis are risk factors for long-term disability and future progressive disease course. These measures are evaluable in clinical practice. In patients with established MS, GM involvement and neurodegeneration are associated with accelerated clinical worsening. Subpial demyelination and slowly expanding lesions are novel indicators of progressive MS.

Conclusions and Relevance  Diagnosis of PPMS is more challenging than diagnosis of RRMS. No qualitative clinical, immunological, histopathological, or neuroimaging features differentiate PPMS and SPMS; both are characterized by imaging findings reflecting neurodegeneration and are also impacted by aging and comorbidities. Unmet diagnostic needs include identification of MRI markers capable of distinguishing PPMS from RRMS and predicting the evolution of RRMS to SPMS. Integration of multiple parameters will likely be essential to achieve these aims

Box 1.

Key Questions and Proposed Magnetic Resonance Imaging (MRI) Features for Identification of Progressive Multiple Sclerosis

Is There Any MRI Feature That Can Support Primary Progressive Multiple Sclerosis (PPMS) and Secondary Progressive Multiple Sclerosis (SPMS) Diagnosis?
  • PPMS
    • Diffuse signal abnormalities in the spinal cord
    • Spinal cord lesions involving the gray matter (GM) and at least 2 white matter (WM) columns (axial plane)
    • Atrophy of the lower portion of the cervical cord
  • SPMS
    • Spinal cord lesions involving the GM and at least 2 WM columns (axial plane)
    • Atrophy of the lower portion of the cervical cord
    • Cord GM atrophy
Are There Specific MRI Features at Disease Onset Able to Predict Disability and a Progressive Course?
  • PPMS
    • Gadolinium-enhancing lesions at baseline
    • Spinal cord lesions at baseline
  • SPMS
    • Number and volume of baseline brain lesions showing hyperintensity on T2-weighted MRI
    • Increase in brain lesion volume showing hyperintensity on T2-weighted MRI during the first 5 y after disease onset
    • At least 2 gadolinium-enhancing lesions at baseline
    • At least 1 spinal cord lesion at baseline
    • At least 1 infratentorial lesion at baseline
    • At least 1 cortical lesion at baseline
    • At least 1 spinal cord lesion within 1 or 3 y after disease onset
    • At least 1 infratentorial lesion within 1 or 3 y after disease onset
    • At least 1 deep WM lesion within 1 y after disease onset
Are There MRI Markers Able to Identify Disability Progression? In Relapse-Onset Multiple Sclerosis, Are There MRI Markers Able to Identify Evolution to SPMS?
  • PPMS
    • New lesions showing hypointensity on T1-weighted MRI
    • Cortical lesion number and volume
    • Baseline GM damage
    • Rate of brain atrophy
  • SPMS
    • Lesion volume on T2-weighted MRI
    • Increase in lesion volume hypointensity on T1-weighted MRI
    • Cortical lesion number and volume
    • Conversion of dirty-appearing WM into focal WM lesions
    • GM volume
    • Rate of brain GM and deep GM atrophy
Are There Distinguishing MRI Features Between PPMS and SPMS?
  • None
Are There Candidate MRI Biomarkers to Identify MS Progression?
  • At least 4 paramagnetic rim lesions
  • Subpial demyelination

According to the 2017 revision of the McDonald criteria, PPMS can be diagnosed in pwMS with at least 12 months of disability progression (retrospectively or prospectively assessed) independent of clinical relapses who also meet 2 of the following 3 criteria: (1) 1 or more lesions showing hyperintensity on T2-weighted MRI characteristic of MS in 1 or more periventricular, cortical or juxtacortical, or infratentorial brain regions; (2) at least 2 lesions in the spinal cord showing hyperintensity on T2-weighted sequences; and (3) cerebrospinal fluid–specific oligoclonal bands.

Diagnosis of SPMS is based on retrospective assessment of progressive disability worsening unrelated to clinical relapses over at least 6 to 12 months.

Clinical identification of MS progression is typically retrospective, challenging, and delayed by months to years after onset. Moreover, clinical examination does not allow early identification of the neurodegenerative phenomena that start from the earliest phases of the disease, several years before the occurrence of overt disability progression.

Discovery of MR markers capable of detecting evolution from RRMS to SPMS remains an unmet need. Multiparametric MRI studies are needed because it is unlikely that a single MR method will be an optimal discriminator.

Novel candidate imaging biomarkers, such as subpial demyelination, and the presence of slowly expanding lesions or PRLs may identify PMS but should be further investigated.

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MouseDoctor

6 comments

  • Not that anyone knows about (the MRI biomarkers, I mean, that distinguish between PPMS and SPMS) but a JAMA Neurology publication gives it the needed attention, I guess. One would imagine that with the progress of technology, and the FDA approval of 7T magnets for clinical use in the USA (I am not sure what goes on for ‘standardized medicine’ in the UK), most Universities would have it. Of course not. We have about 30 odd, perhaps that is the right number, centers wherein the 7T MRI is in use. What of the rest of us ?

    If they say we found this, or that, the rest of us blink. We can only ask Qs and that’s it.

    So, how will the rest of the world (read, poor) with no 7T even make discoveries as they relate to RRMS or PPMS ? Of course we have 11T and perhaps 14 T in the research domain. SO, sans technology, biomarkers do not jump at you is my point.

    • j.R.A., Pardon my mood in advance, the dark winter has only begun . . .yet people here, seemingly reasonable people, go maskless in stores in so called “protest”.. and demonstrate to me that they feel my life is less than the value they placed on this so called “liberty”. It is clear, however, that you care about me and pwms. But I feel your pining for a 7T brain mri machine might not help the management of MSers at present. Did any of the measurements from this cited article come from a 7T MRI? My understanding is that the higher power mri prevents looking at deep parts of the brain, unless it’s on a post mortem glass slide. It also has raised safety concerns in medical community. https://doi.org/10.1148/radiol.2019182742 . Thus, I gently suggest to put your passion in directly benefiting pwms with GM lesions (per article) with “detection validation and standardization at the individual patient level”. Hell, Go even further, and Give us pwms a universally accepted measurement of atrophy per area of brain and rate measurement. That is worth pining over!

  • MD, Dr Beaber tweeted about this study this morning. Given that there are no distinguishing MRI features between PPMS and SPMS, would this add weight to the argument that MS is one disease?

    • I think so. It is probably up to the MS community to push this as medics and academics are busy treating anddoing research.

  • Number and volume of baseline brain lesions showing hyperintensity on T2-weighted MRI
    Increase in brain lesion volume showing hyperintensity on T2-weighted MRI during the first 5 y after disease onset
    At least 2 gadolinium-enhancing lesions at baseline
    At least 1 spinal cord lesion at baseline
    At least 1 infratentorial lesion at baseline
    At least 1 cortical lesion at baseline
    At least 1 spinal cord lesion within 1 or 3 y after disease onset
    At least 1 infratentorial lesion within 1 or 3 y after disease onset
    At least 1 deep WM lesion within 1 y after disease onset

    Looks like an supermarket list (dont forget the matches 🙂 )

    Obrigado por teres escarafunchado este

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