ClinicSpeak: grey matter brain lesions and relapses

Have you ever had a gray matter relapse? #ClinicSpeak #MSBlog #MSResearch

“You have heard me state many times that the current dogma that MS is a white matter disease is wrong. Pathology studies show that at least half the MS disease burden is found in the cortical and deep gray matter. MS is therefore a whole brain, or a whole central nervous system, disease. The study below reports 5 cases who have cortical relapses with lesions on MRI in the relevant area of the brain to explain the particular symptoms and signs experienced by each MSers concerned. All these MSers had quite extensive cortical syndromes and the lesions were large enough to be seen on MRI. We know that >90% of the cortical lesions are not seen on MRI hence we are missing the majority of lesions with our current imaging protocols; hence my iceberg analogy of MS. The real question is what about cortical lesions that are too small to be seen on MRI; why can’t they cause relapses, in particular minor relapses? We are almost certain that the hidden burden of MS is occurring in the gray matter and is associated with accelerated brain atrophy, cognitive impairment, fatigue, depression and anxiety. This is why we need to move beyond NEDA (no evident disease activity) and reset our treatment target to focus on end-organ damage (NEDA-4 and NEDA-5). If I had MS I would want to be NEDA and in addition have my brain atrophy rate and spinal fluid neurofilament levels normalised. Wouldn’t you? If you answer yes to the latter then you need to realise that on average this will happen more frequently with high efficacy therapies compared to low or intermediate efficacy therapies.”

Puthenparampil et al. Cortical relapses in multiple sclerosis. Mult Scler. 2015 Mar. pii: 1352458514564483.

BACKGROUND: MS is a white and grey matter disease of the central nervous system (CNS). It is recognized that cortical damage (i.e. focal lesions and atrophy) plays a role in determining the accumulation of physical and cognitive disability that is observed in MSers with progressive MS. To date, an association of cortical lesions with clinical relapses has not been described.

RESULTS: We report clinical and magnetic resonance imaging (MRI) findings of five relapsing-remitting MS (RRMS) MSers who had clinical relapses characterized by the acute appearance of cortical symptoms, due to the development of large, snake-like, cortical inflammatory lesions. Symptoms were: acute Wernicke’s aphasia mimicking stroke; agraphia with acalculia, not associated to a motor deficit nor linguistic disturbance; hyposthenia of the left arm, followed by muscle twitching of the hand, spreading to arm and face; acute onset of left lower limb paroxysmal hypertonia; and temporal lobe status epilepticus, with psychotic symptoms.

CONCLUSIONS: Cortical relapses may occur in MS. MRI examination in MS should include sequences, such as double inversion recovery (DIR) or phase sensitive inversion recovery (PSIR), that are aimed at visualizing cortical lesions, especially in the presence of symptoms of cortical dysfunction. Our observation further stresses and extends the clinical relevance of cortical pathology in MS.

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


  • If I had MS I would want to be NEDA and in addition have my brain atrophy rate and spinal fluid neurofilament levels normalised.

    I couldn't agree more. As an alemtuzumab recipient I have annual MRIs. However, I think they are used for identifying inflammation / disease activity rather than brain atrophy. I haven't been offered the option of having my neurofilament levels checked. While undertaking monitoring / measuring is fine, I do worry that the monitoring / measuring techniques are not being matched by treatment options i.e my neuro would probably offer me another dose of alemtuzumab – there isn't really any option. What I'd like is a daily pill to protect my nervous system from further damage (neuroprotective therapy).

  • Prof G – I agree with you that it would be good to get atrophy/neurofilament levels tracked. Is there any prospect of me getting this under the NHS at present? If not, is it available privately and, if so, is it a bank breaker?

    • Re: "I agree with you that it would be good to get atrophy/neurofilament levels tracked. Is there any prospect of me getting this under the NHS at present? If not, is it available privately and, if so, is it a bank breaker?"

      We are about to start implementing brain atrophy measurements into clinical practice. We are still in debating how we will use them to guide clinical decision making and what threshold of change, and over what period of time, is necessary to make decisions. Although we are using spinal fluid neurofilament levels in clinical trials we are not using them in clinical practice yet. Interestingly, several clinics in Sweden are using neurofilament levels to guide clinical decision-making.

    • Any chance you could post detailing how you'll be implementing this? Then I can share it with my neuro and ask him to extend it to me. I'm sure it would be useful for lots of others to do the same too?

  • Yep, agree with my fellow posters.

    I would also wish the OCT to be driven forward as a diagnostic tool and available to MSers for free and not just for patients with an eye disease.

    • Great but again not so great – so maybe the Rowling centre could advertise/recomend it to other centres in the UK and abroad? I talked to my (quite young) neuro and she had not heard of it at all – mind you she had been working before at a clinic.

      I feel that with some diagnostic tools and discoveries there is a communication problem which could be solved if EMA started recomending things faster to all doctors/nurses as their guidelines.

By Prof G



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