Thursday, 30 October 2014

ClinicSpeak: when does MS actually begin?

How long is the asymptomatic period of MS? #ClinicSpeak #MSBlog #MSResearch

"The data below was presented at last year's AAN meeting in San Diego and I have been presenting it in my talks ever since. It supports my MS dementia rebranding exercise. In Argentina all people do standardised examinations in the last 3 years of school. If someone develops a clinically isolated syndrome (CIS) after leaving school you can go back an look at their school performance and compare them to matched control subjects. What this study shows that cognitive performance in the last 3 years of school is poorer in subjects presenting with CIS after school compared to appropriately matched control subjects. Interestingly, cognitive performance was worse in subjects the closer their CIS presentation occurred after school. It appears as if the effect on cognition was noted up to 10 years after leaving school. What does this mean? It is telling us that MS has a long asymptomatic period that is obviously culling cognitive ability years before the first clinical attack. This is similar to the prodrome, called minimal cognitive impairment (MCI), that is seen in people who go onto develop Alzheimer's disease."


"Should you be surprised by these findings? Not really, these observations are congruent with several other observations. Firstly, most people presenting with CIS have several older lesions on their MRI indicating that the disease has been presented for sometime prior to the new lesion causing their CIS. People with both clinically-isolated and radiologically-isolated syndromes (RIS) often have pre-existing brain atrophy and cognitive impairment indicative of the disease being present for a period of time. Children presenting with CIS, or MS, have smaller brains than children presenting with acute disseminated encephalomyelitis (ADEM) indicating that MS has an asymptomatic period affecting brain development and ADEM, a monophasic disease, does not."



"How long is the asymptomatic period of MS? These data would suggest it being years and possibly loner than 10 years. This sets a challenge for us to try and diagnose MS in the presymptomatic phase so that we can try intervene earlier in the course of the disease. This was one of the drivers of our so called endophenotype project. The question is would someone start treatment before they have a clinical attack? This is happening already; I am aware of several neurologist across the globe who has patients with RIS (asymptomatic MS) on DMTs. Please note treating RIS would not be allowed in the UK and at presenting RIS is not part of the diagnostic criteria of MS. I suspect this will change in the future; MS is a biological disease before it is a clinical disease!"

Epub: Sinay et al. School performance as a marker of cognitive decline prior to diagnosis of multiple sclerosis. Mult Scler. 2014. pii: 1352458514554054.

BACKGROUND: For many years, cognitive impairment has been established as a well-known symptom of MS. Moreover, we know that it was present even at the beginning of the disease.

OBJECTIVE: In this case-control study, we decided to evaluate whether there is an impairment of cognitive functions even before onset in those people who will eventually suffer from multiple sclerosis.


METHODS: We evaluated the overall school performance, and particularly school performance in math and language in a group of people who would later develop the disease and we compared our findings with a control group.


RESULTS: We found that school performance was poorer in subjects who were to become patients. And we found that the later the start of the first symptom, the better the qualifications.


CONCLUSION: Testing a premorbid cognitive deficit by a validated indirect evaluation method allowed us to verify that there was evidence of neurological compromise even before a clinical diagnosis or the completion of the first magnetic resonance imaging in patients who would then suffer from multiple sclerosis.

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IV IG making false positives for JC Virus

Kister I, Kuesters G, Chamot E, Omari M, Dontas K, Yarussi M, Subramanyam M, Herbert J. IV immunoglobulin confounds JC virus antibody serostatus determination. Neurol Neuroimmunol Neuroinflamm. 2014 Sep 18;1(3):e29. doi: 10.1212/NXI.0000000000000029. eCollection 2014 Oct.

OBJECTIVE:To determine the impact of therapeutic infusion of IV immunoglobulin (IVIg) on John Cunningham virus antibody (JCV Ab) serostatus and level in serum.
METHODS:  We carried out a retrospective analysis of serum levels of JCV Ab among STRATIFY-2 trial enrollees from 2 multiple sclerosis centers who were exposed to IVIg during the trial. For the subset of eligible patients, we estimated mean linear trends while on IVIg and after stopping IVIg with a linear mixed-effects model.
RESULTS: The JCV Ab seropositivity rate in the group of patients that was recently exposed to IVIg was 100%, which is significantly higher than in the IVIg-naive population (58%, p < 0.001). The seropositivity rate in the patient group with remote IVIg exposure was similar to that in the IVIg-naive population (67%, p = 0.68, Fisher exact test). The slope of the linear trend line after stopping IVIg decreased significantly by -0.310 units per 100 days (95% confidence interval, -0.611 to -0.008; p = 0.04).
CONCLUSIONS: Recent IVIg exposure is invariably associated with JCV Ab seropositivity. After stopping IVIg, JCV Ab levels tend to decrease with time, and seroreversion to innately Ab-negative status can occur.


Intravenous immunoglobulin is a the antibodies from a large pool  of over a thousand people and if you get this for your MS, then it gives you the potential for a false positive anti-JC virus test,