Sunday, 25 February 2018

Pregnancy

Portaccio E, Annovazzi P, Ghezzi A, Zaffaroni M, Moiola L, Martinelli V, Lanzillo R, Brescia Morra V, Rinaldi F, Gallo P, Tortorella C, Paolicelli D, Pozzilli C, De Giglio L, Cavalla P, Cocco E, Marrosu MG, Patti F, Solaro C, Bellantonio P, Uccelli A, Laroni A, Pastò L, Giannini M, Trojano M, Comi G, Amato MP; MS Study Group of the Italian Neurological Society. Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: I: Foetal risks. Neurology. 2018. pii: 10.1212/WNL.0000000000005067

OBJECTIVE:To assess fetal risk after pregnancy exposure to natalizumab in women with multiple sclerosis (MS), with a specific focus on spontaneous abortion (SA) and congenital anomalies (CA).
METHODS:Data of all pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab and referring to 19 participating sites were collected and compared with those of pregnancies in untreated patients and patients treated with injectable immunomodulatory agents. Rates of SA and CA were also compared with those reported in the Italian population. Multivariable logistic and linear regression models were performed.
RESULTS:A total of 92 pregnancies were tracked in 83 women. In the multivariable analysis, natalizumab exposure was associated with SA (odds ratio [OR] 3.9, 95% confidence interval [CI] 1.9-8.5, p < 0.001). However, the rate of SA (17.4%) was within the estimates for the general population, as well as the rate of major CA (3.7%). Moreover, exposure to natalizumab and interferon-β (IFN-β) was associated with lower length and weight of the babies (p < 0.001).
CONCLUSION:Our results showed that natalizumab exposure to up 12 weeks of gestation is associated with an increased risk of SA, although within the limits expected in the general population, whereas the risk of CA needs further investigation. Taking into account the high risk of disease reactivation after natalizumab suspension, pregnancy could be planned continuing natalizumab while strictly monitoring conception.

Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: II: Maternal risks.Portaccio E, Moiola L, Martinelli V, Annovazzi P, Ghezzi A, Zaffaroni M, Lanzillo R, Brescia Morra V, Rinaldi F, Gallo P, Tortorella C, Paolicelli D, Pozzilli C, De Giglio L, Cavalla P, Cocco E, Marrosu MG, Solaro C, Uccelli A, Laroni A, Pastò L, Giannini M, Trojano M, Comi G, Amato MP; MS Study Group of the Italian Neurological Society.
Neurology. 2018 Feb 7. pii: 10.1212/WNL.0000000000005068.

OBJECTIVE:To assess the risk of disease reactivation during pregnancy after natalizumab suspension in women with multiple sclerosis(MS).
METHODS:Data of all pregnancies occurring between 2009 and 2015 in patients with MS treated with natalizumab and referring to 19 participating sites were collected and compared with those of pregnancies in untreated patients and patients treated with injectable immunomodulatory agents through a 2-factor repeated measures analysis. Predictors of disease activity were assessed through stepwise multivariable logistic regression models.
RESULTS: A total of 92 pregnancies were tracked in 83 women receiving natalizumab. Among these pregnancies, 74 in 70 women resulted in live births, with a post-partum follow-up of at least 1 year, and were compared with 350 previously published pregnancies. Relapse rate during and after pregnancy was higher in women treated with natalizumab (p < 0.001). Longer natalizumab washout period was the only predictor of relapse occurrence during pregnancy (p = 0.001). Relapses in the post-partum year were related to relapses during pregnancy (p = 0.019) and early reintroduction of disease-modifying drugs (DMD; p = 0.021). Disability progression occurred in 16.2% of patients and was reduced by early reintroduction of DMD (p = 0.024).
CONCLUSIONS: Taken as a whole, our findings indicate that the combination of avoiding natalizumab washout and the early resumption of DMD after delivery could be the best option in the perspective of maternal risk. This approach must take into account possible foetal risks that need to be discussed with the mother and require further investigation.


You can all read this

Saturday, 24 February 2018

Education PNS and CNS axons

Peripheral nervous system and central nervous system nerve axons

A nerve that we see in the peripheral nervous system (PNS) or a white-matter ‘tract’ in the central nervous system (CNS) is composed of many axons. The axons are elongated extensions of individual nerve cells, and they are structures specialized for signalling over distance. Let me try to explain.

When you see a peripheral nerve in a limb, from the outside, it is protected by a robust sheath, made of connective tissue. This sheath gives the peripheral nerve a degree of robustness and stretchiness. 

Peripheral nerves are unharmed by being stretched a bit, and to a surprising degree they move or glide past adjacent tissues for example at the carpal tunnel, when we move and bend our limbs, quite normally. Held within that stretchy coating are the nerve axons, either sending signals towards the spinal cord or the brain, in the form of sensory input, or away from the spinal cord or brain to provide some motor function be it muscle contraction, or secretion. 

The same is not true of nerves protected inside the skull and spinal column. 

The nerve fibres within the central nervous system are not covered in a stretchy coat in the same way as in the periphery, and these axons are usually to be found in tracts, notable for their white appearance in dissection, the ‘white matter’ that most people have heard about. These nerve fibres are known to signal over distance by sending nerve impulses from one part of the CNS to another, or also down the spinal cord to control our body movements. 

They are embedded in the three dimensional anatomical structure of the brain and spinal cord. Like the axons in peripheral nerves they are accompanied by nearby blood vessels and capillaries that provide the necessary oxygen and glucose that allow them to function.


The median nerve (in red) is an example of a long peripheral nerve innervating the arm and hand. It is a mixed nerve, with sensory and motor function. It innervates the hand via the carpal tunnel at the wrist. The main stem of the nerve is flexible and moves around quite a lot as we move and bend our arm. Central axons in the brain or spinal cord are not able to move independently of the tissue around them, and are held fast

#ThinkHand Awareness Speech

My speech from our #ThinkHand Awareness event on Thursday night. 



Friday, 23 February 2018

HSCT and T cells and MS and memory B cells

What cells are important to target in HSCT?

TeamG in the News...used for Crowd funding

ProfG and DrK were in the media yesterday as they launched their #Thinkhand campaign.

Yep this is old news on the blogsphere, but the Evening Standard (Local London Newspaper) picked up the story and pulled a fast one


Thursday, 22 February 2018

Putting the CART before the horse: could CAR-T cells be a last-resort therapy in MS to rival HSCT?

First off, apologies my long winter hibernation from the blog. As you may have gathered (if anyone is paying close attention to my blogging habits) I'm no longer full-time at BartsMS, and have been working in mental health down the road at Mile End. There are loads of interesting things to say about the overlap between MS and mental health, lots of which have been discussed before on the blog. 

#ThinkHand: Today is MS Hand Awareness Day

We are hosting our #ThinkHand Awareness event tonight. The good news is that Shift.ms will be there to help promote the campaign. The following are some YouTube clips, from their reporters, explaining the campaign and how you can help. 

Thank you Shift.ms for helping and spreading hope for the million-plus people who have MS and are using a wheelchair.




Wednesday, 21 February 2018

Barts Health CSF Neurofilament light chain (NfL) request


As promised, any clinician based in the UK can request the neurofilament light chain for Multiple Sclerosis. Your hospital laboratory would need to discuss the transfer of you CSF sample to our lab:

Dr David Holden
Centre for Neuroscience and Trauma,
Queen Mary University of London,
4 Newark St
London
E1 4AT

Email: d.w.holden@qmul.ac.uk

A sample request form is below:



The final report that you receive will look something like this:



If there are particular questions with regard to sample volume, storage and transport Dr Holden will be able to answer them.

Vitamin C for myelination

What has vitamin C got to do with MS?


Our Prime Minister has the decency to send her apologies

We are hosting our #ThinkHand awareness event tomorrow night. We were hoping to get Theresa May to attend and endorse the event. At least she responded. JK Rowling didn't even acknowledge our invitation. Very poor form?