Monday 3 September 2018

Should Prof G do less blogging and more walking the talk?

Did you know that approximately 25% of people diagnosed with a radiologically-isolated syndrome (RIS), or asymptomatic MS, already cognitive impairment and smaller brains? This indicates that even before MS has been diagnosed the disease processes are already causing subclinical damage to brains of people destined to develop full-blown MS in the future. The reason you are not aware of this is that the brain has spare capacity, reserve or some redundancy to allows you to compensate for this early damage.

What about hand function (#ThinkHand)?

The study below takes these observations one step further and show that RISers also have deficits in hand function that they are not aware of. Using a super intelligent glove with sensors these researchers showed that finger-to-thumb opposition at maximum speed and paced two-handed movements were abnormal when compared to control or normal subjects. These abnormalities of hand function were related to the number of lesions on MRI or MS disease pathology. In all likelihood, these RISers would not be aware of these abnormalities, unless they were using their hands at a very high level, for example, professional musicians. Or then again they may simply ignore them as something else. Isn’t this disease scary?

What are the implications of this research for the MS community? Firstly, it argues for us changing the diagnostic criteria to allow us to diagnose MS earlier, in the RIS phase, so that we can offer these patients treatment. Some of the naysayers will say that by allowing MS to be diagnosed earlier we will misdiagnose too many people with MS who don’t have the disease. I am not sure if this is correct. If we developed new diagnostic criteria for asymptomatic MS and tested them properly in a prospective group of RISers and compared them to the gold standard, i.e. pathological diagnosed MS, we could assess the sensitivity and specificity of the criteria and their positive and negative predictive value to address this criticism.

Did you know that the various renditions of the current MS diagnostic criteria have never been validated against a pathological gold-standard? We can make some assumptions that they do okay based on the findings of one or two post-mortem studies, but we can’t be confident about their performance outside areas of high MS prevalence. Secondly, this study supports using hand function as an outcome measure in clinical trials, it seems that if we use sensitive tests of hand function we may be able to use these measures to assess DMTs that delay worsening or even improve hand function.

Two things that I could potentially do as a result of this paper. The first is to walk the talk and write a proposal for a new set of MS diagnostic criteria, which will include asymptomatic MS. The proposal will need to include a study to validate the new criteria against a pathological gold-standard and to test the criteria in high, intermediate and low prevalence areas. A pathological (biopsy or post-mortem) gold standard is required because none of the previous MS diagnostic criteria has ever been validated in this way. The reason for studying the performance of the new criteria in different MS prevalence areas is that the positive and negative predictive values of diagnostic criteria, i.e. their ability for them get the diagnose right depends on how common or rare MS is and how common or rare MS mimics are in the particular area. Against me walking the talk is that I am not sure if I have it in me to take on the MS community in terms of redefining MS.

The other action point that I will take away from this research is that we should try and include this glove as part of our ORATORIO-HAND and CHARIOT-MS studies. We could do small add-on studies to test the utility of the glove and compare it to the 9HPT and the ABILHAND PROM. Another proposal would be to use the glove to assess the impact that neuro-rehabilitation has on hand function. Because the glove has a much lower floor effect, i.e. it even detects abnormalities in asymptomatic MSers, it could potentially be a much better outcome measure in disease improvement trials.

Lot’s to do and not enough time to do it all. Maybe less talking (less blogging) and more walking ;-)

BACKGROUND: An engineered glove measuring finger motor performance previously showed ability to discriminate early-stage multiple sclerosis (MS) patients from healthy controls (HC). Radiologically isolated syndrome (RIS) classifies asymptomatic subjects with brain MRI abnormalities suggestive of multiple sclerosis.

METHODS: We assessed 17 asymptomatic subjects with radiologically isolated syndrome (RIS) and 17 HC. They performed finger-to-thumb opposition sequences at their maximal velocity, metronome-paced bimanual movements and conventional and diffusion tensor MRI.

RESULTS: Subjects with RIS showed lower (p=0.005) maximal velocity and higher (p=0.006) bimanual coordination impairment than HC. In RIS, bimanual coordination correlated with T2-lesion volume, fractional anisotropy and radial diffusivity in the white matter.

CONCLUSIONS: These findings point out the relevance of fine hand measures as a robust marker of subclinical disability.

By: Gavin Giovannoni

CoI: none in relation to this post