Thursday, 20 July 2017

BrainHealth

Today in the News you may hear about brain health to help protect against Dementia from Alzheimer's. However, these are all relevant to MS too
There are 9 things mentioned that may help 

The nine risk factors include:
  • Less childhood education
  • Hearing loss
  • Hypertension
  • Obesity
  • Smoking
  • Diabetes
  • Depression
  • Physical inactivity
  • Social isolation
Potential risk factors:

  • Pollution
  • Visual loss
We all know that an active body and and active brain, helps protect against ill-health, 

If I asked you to think of things that promote brain health, you could write this on the bad of a fag-packet, which you should throw away as you shouldn't be smoking.

The interesting ones to me are hearing loss but this makes sense because hearing and vision are essential part of sensory input that is going to keep your brain active making new connections.

However, if you look at the list above, many of them are all inter-connected e.g. physical activity, obesity, diabetes.

Please note you can do all the unhealthy things and not get dementia and you can be as healthy as possible and get dementia, the list above are risk factors that are modifiable by life style, adopt them they reduce your risk but do not prevent risk.

MS Blog of Year 2017

We received notice that we were one of the Healthline's 
Best MS Blogs of the Year

Here is the list (CLICK). Be warned this site contains adverts and this has nothing to do with us.

psychiatric disorders in children

Psychiatric disorders in children with demyelinating diseases of the central nervous system.Pakpoor J, Goldacre R, Schmierer K, Giovannoni G, Waubant E, Goldacre MJ.
Mult Scler. 2017 Jul 1:1352458517719150. doi: 10.1177/1352458517719150. [Epub ahead of print]

INTRODUCTION:

The profile of psychiatric disorders associated with multiple sclerosis (MS) may differ in children. We aimed to assess the risk of psychiatric disorders in children with MS and other demyelinating diseases, and vice versa.

PATIENTS AND METHODS:

We analyzed linked English Hospital Episode Statistics, and mortality data, 1999-2011. Cohorts were constructed of children admitted with MS and other central nervous system (CNS) demyelinating diseases. We searched for any subsequent episode of care with psychiatric disorders in these cohorts and compared to a reference cohort.

RESULTS:

Children with CNS demyelinating diseases had an increased rate of psychotic disorders (rate ratio (RR) = 5.77 (95% confidence interval (CI) = 2.48-11.41)); anxiety, stress-related, and somatoform disorders (RR = 2.38 (1.39-3.81)); intellectual disability (RR = 6.56 (3.66-10.84)); and other behavioral disorders (RR = 8.99 (5.13-14.62)). In analysis of the paediatric MS cohort as the exposure, there were elevated rates of psychotic disorders (RR = 10.76 (2.93-27.63)), mood disorders (RR = 2.57 (1.03-5.31)), and intellectual disability (RR = 6.08 (1.25-17.80)). In reverse analyses, there were elevated rates of a recorded hospital episode with CNS demyelinating disease after a previous recorded episode with anxiety, stress-related, and somatoform disorders; attention-deficit hyperactivity disorder (ADHD); autism; intellectual disability; and other behavioral disorders.

CONCLUSION:

This analysis of a national diagnostic database provides strong evidence for an association between pediatric CNS demyelinating diseases and psychiatric disorders, and highlights a need for early involvement of mental health professionals.

Children who get MS are at a 6 times risk of getting psychiatric issues,

Wednesday, 19 July 2017

#TeachSpeak: our belief in small numbers

Why do we have so many cognitive frailties; e.g. our belief in small numbers? #TeachSpeak

I want to restate what I said yesterday in a comment that the mistake I made, and many others are making, when considering the cancer risk with ocrelizumab is that we are over interpreting data based on very small numbers. To understand this phenomenon I suggest you read the classic, and probably one of the most influential, papers in psychology by Tversky and Kahneman on the 'belief in the law of small numbers'. The problem with the human brain is that we believe in small numbers. What we really need is slow thinking and large numbers, for that we will have to wait some time for more safety data to emerge regarding rare adverse events. 

One of  the reasons for keeping the survey below open so long is that I want a large sample; I need several hundred respondents for the results to have face validity and, obviously, to move away from small numbers.  


TVERSKY & KAHNEMAN. BELIEF IN THE LAW OF SMALL NUMBERS. Psychological Bulletin, 1971, Vol. 76, No. 2. 105-110. 

People have erroneous intuitions about the laws of chance. In particular, they regard a sample randomly drawn from a population as highly representative, that is, similar to the population in all essential characteristics. The prevalence of the belief and its unfortunate consequences for psvchological research are illustrated by the responses of professional psychologists to a questionnaire conceming research decisions.


CoI: multiple

Neutrophil loss after alemtuzumab

Gait├ín MI, Ysrraelit MC, Correale J. Neutropenia in Patients With Multiple Sclerosis Treated With Alemtuzumab. JAMA Neurol. 2017 Jul 17. doi: 10.1001/jamaneurol.2017.1456


We all know that alemtuzumab depletes lymphocytes and if you don’t, you should have read our recent papers. 

Both cladribine and alemtuzumab may effect MS via B-cell depletion.Baker D, Herrod SS, Alvarez-Gonzalez C, Zalewski L, Albor C, Schmierer K. Neurol Neuroimmunol Neuroinflamm. 2017 Jun 5;4(4):e360.


Interpreting Lymphocyte Reconstitution Data From the Pivotal Phase 3 Trials of Alemtuzumab.Baker D, Herrod SS, Alvarez-Gonzalez C, Giovannoni G, Schmierer K. JAMA Neurol. 2017 Jun 12. doi: 10.1001/jamaneurol.2017.0676. [Epub ahead of print]

However, CD52 is expressed on a number of other cells like monocytes, which get transiently depleted. It is also found on sperm. 

It is also expressed on by polymorphonuclear cells. These form about 70% of your white blood cells. These are part of your first line of defense from infection. This is the main reason why you are taken out of circulation for 20-30 days after HSCT, as you have to wait for your neutrophils to be repopulated. They only live for about 5 days and then die to be replaced by new ones.

This report talks about polymorphonuclear neutrophils and says to their surprise that alemtuzumab causes loss of neutrophils in some people with MS and this hasn’t been reported before. 

Smith A, Couvillion R, Zhang R, Killackey M, Buell J, Lee B, Saggi BH, Paramesh AS.Incidence and management of leukopenia/neutropenia in 233 kidney transplant patients following single dose alemtuzumab induction. Transplant Proc. 2014 Dec;46(10):3400-4.

In MS maybe not but anyway, they report on two cases of people with MS that have severely depleted their neutrophils. This is means the people were susceptible to infection and in this paper they treat the neutrophil deficiency with granulocyte (neutrophils are a type of granulocyte as they have neutral granules compared to those with alkali granules in a basophil or acid granules in an eosinophil important as neutrophils) growth factor. So if this is interesting as a safety perspective…then surely it is interesting to know how common this event it is following use in MS.

So yesterday when I saw the paper, I trawled through the unpublished phase III trial alemtuzumab data set supplied by the European Medicines agency, wrote and submitted the paper for review and publication. So thanks for that.

So you and your neuros are aware, Neutrophils are not depleted to a great extent by alemtuzumab in most people, transient minor depletion is common in 20-25% of people, but about 3% of people develop severe neutropenia (loss of neutrophils) and this is transient in most people. You could check for this by monitoring your blood counts after alemtuzumab.