Sunday, 19 August 2018

ProfG a Week in TwitterLand

ProfG has taken to twitter to comment on posts.Should we consider a feature on his comments on the blog as it is is clear many people can't we bothered with Twitter?

Gavin GiovannoniThis study suggest that the anti-JC virus antibody index will be difficult to interpret and use to risk profile MSers on rituximab or ocrelizumab as it affects antibody production.
Anti-JC virus antibody index changes in rituximab-treated multiple sclerosis patients.
Baber U, Bouley A, Egnor E, Sloane JA. J Neurol. 2018 Aug 14. doi: 10.1007/s00415-018-8996-3. [Epub ahead of print]

Gavin GiovannonAgeing is a big problem in MS. This paper suggest it contributes to falls as well as cerebellar and cognitive dysfunction in MS.
Cerebellum and cognition in multiple sclerosis: the fall status matters.Schreck LM, Ryan SPP, Monaghan PG.J Neurophysiol. 2018 Aug 15. doi: 10.1152/jn.00245.2018. [Epub ahead of print]

Gavin Giovannoni.As a community of MS stakeholders we need to take care to produce better and more practical guidelines, particularly in relation to lifestyle issues such as physical activity. A systematic critical review of physical activity aspects in clinical guidelines for multiple sclerosis. Geidl W, Gobster C, Streber R, Pfeifer K.Mult Scler Relat Disord. 2018 Aug 3;25:200-207.


Gavin Giovannoni MSers with hypertension and/or heart disease have a much greater loss of brain volume than MSers without these comorbid diseases. Not surprising considering what we know about hypertension and brain reserve. Do you know your blood pressure?Hypertension and heart disease are associated with development of brain atrophy in multiple sclerosis: a 5-year longitudinal study.Jakimovski D, Gandhi S, Paunkoski I, Bergsland N, Hagemeier J, Ramasamy DP, Hojnacki D, Kolb C, Benedict RH, Weinstock-Guttman B, Zivadinov R.Eur J Neurol. 2018 Aug 13. doi: 10.1111/ene.13769. [Epub ahead of print]

Gavin Giovannoni‏ Instilling a small amount of ice water into the bladder of MSers and measuring the change in pressure allows urologists to diagnosis overactivity of the detrusor muscle. Low tech but potentially useful. Ice water test in multiple sclerosis: A pilot trail.Hüsch T, Reitz A, Ulm K, Haferkamp A. nt J Urol. 2018 Aug 13. doi: 10.1111/iju.13786. [Epub ahead of print]

Gavin Giovannoni‏ Another piece of dogma bites the dust. #NeuroSpeak Visual prognosis in seronegative idiopathic optic neuritis finally elucidated: as bad as that in anti-AQP4-Ab (+) optic neuritis. Visual prognosis in seronegative idiopathic optic neuritis finally elucidated: as bad as that in anti-AQP4-Ab (+) optic neuritis. Akaishi T, Nakashima I. Eur J Neurol. 2018 Aug 13. doi: 10.1111/ene.13772. [Epub ahead of print]

Gavin Giovannoni Another depressing study showing the impact a diagnosis of MS has on young adults. Why aren't we doing more to prevent this disease. 
Young adults' adjustment to a recent diagnosis of multiple sclerosis: The role of identity satisfaction and self-efficacy. Calandri E, Graziano F, Borghi M, Bonino S. isabil Health J. 2018. pii: S1936-6574(18)30139-0.

Gavin Giovannoni‏  A paper showing that cerebrospinal fluid GAP-43 (a recovery marker) is raised in early multiple sclerosis. Will it be down in more advanced MS?. Cerebrospinal fluid GAP-43 in early multiple sclerosis. Rot U, Sandelius Å, Emeršič A, Zetterberg H, Blennow K.Mult Scler J Exp Transl Clin. 2018 4(3):2055217318792931.

Gavin Giovannoni‏ No wonder the early burden of MS is related cognitive impairment. The shredder damages connectivity in the MS brain. Are you surprised? Another reason to treat early and effectivelyMagnetic resonance markers of tissue damage related to connectivity disruption in multiple sclerosis. Solana E, Martinez-Heras E, Martinez-Lapiscina EH, Sepulveda M, Sola-Valls N, Bargalló N, Berenguer J, Blanco Y, Andorra M, Pulido-Valdeolivas I, Zubizarreta I, Saiz A, Llufriu S.Neuroimage Clin. 2018;20:161-168.

Gavin Giovannoni‏ Another elephant in the room (immunosuppression) is making things crowded. #ClinicSpeak Infectious complications of MS DMTs: implications for screening, prophylaxis, and management. Infectious Complications of Multiple Sclerosis Therapies: Implications for Screening, Prophylaxis, and Management.Epstein DJ, Dunn J, Deresinski S.Open Forum Infect Dis. 2018 ;5(8):ofy174.

Gavin Giovannoni‏ TEVA fights back and shows major physicochemical, biological, functional and toxicological differences between the European follow-on glatiramer acetate compared to Copaxone. Will this impact efficacy?Physicochemical, biological, functional and toxicological characterization of the European follow-on glatiramer acetate product as compared with Copaxone. Melamed-Gal S, Loupe P, Timan B, Weinstein V, Kolitz S, Zhang J, Funt J, Komlosh A, Ashkenazi N, Bar-Ilan O, Konya A, Beriozkin O, Laifenfeld D, Hasson T, Krispin R, Molotsky T, Papir G, Sulimani L, Zeskind B, Liu P, Nock S, Hayden MR, Gilbert A, Grossman I.eNeurologicalSci. 2018 May 30;12:19-30.

Gavin Giovannoni‏ Is creating a walled garden the way to deal with fake news in the MS space? Influencers and health-related professional participation on the Web: A pilot study on a social-network of MS
Fake news, influencers and health-related professional participation on the Web: A pilot study on a social-network of people with Multiple Sclerosis. Lavorgna L, De Stefano M, Sparaco M, Moccia M, Abbadessa G, Montella P, Buonanno D, Esposito S, Clerico M, Cenci C, Trojsi F, Lanzillo R, Rosa L, Morra VB, Ippolito D, Maniscalco G, Bisecco A, Tedeschi G, Bonavita S.Mult Scler Relat Disord. 2018 Jul 31;25:175-178. 

Gavin Giovannoni‏ Mental health is a big problem for MSers. Another hidden problem highlighting how large the burden of disease we are missing by focusing on the physical. Factors associated with perceived need for mental health care in multiple sclerosis. Orr J, Bernstein CN, Graff LA, Patten SB, Bolton JM, Sareen J, Marriott JJ, Fisk JD, Marrie RA; CIHR Team in Defining the Burden and Managing the Effects of Immune-mediated Inflammatory Disease.Mult Scler Relat Disord. 2018;25:179-185
Gyllensten H, Kavaliunas A, Alexanderson K, Hillert J, Tinghög P, Friberg E. Mult Scler J Exp Transl Clin. 2018;4(3):2055217318783352.

 Gavin Giovannoni‏  MRI and CIS outcomes. Surely baseline lesion number simply indicates that CISers have had asymptomatic MS longer, hence the MS-shredder has had more time to reduce brain reserve and hence they do worse? How do we capture the time vector? Cerebrospinal fluid GAP-43 in early multiple sclerosis. Rot U, Sandelius Å, Emeršič A, Zetterberg H, Blennow K.Mult Scler J Exp Transl Clin. 2018;4(3):205521731879293

Gavin Giovannoni‏ We now have the biomarkers for microglial activation. The question is whether or not inhibiting microglia will make MS better or worse? I suspect worse. The microglial response in MS may be a positive not a negative.Comparison of two different methods of image analysis for the assessment of microglial activation in patients with multiple sclerosis using (R)-[N-methyl-carbon-11]PK11195. Kang Y, Schlyer D, Kaunzner UW, Kuceyeski A, Kothari PJ, Gauthier SA. LoS One. 2018;13(8):e0201289.

Saturday, 18 August 2018

Evidence against oligoclonal bands being important?

As you may realise, I am sometimes critical of my colleagues who tend to follow dogma, without question.

This of course does me no favours with my colleagues. Maybe I should just say everything is "Great" or "Super", like I'm part of  some 1970s Sitcom :-0

Friday, 17 August 2018

Guest post: Does degradation of brain fats cause MS?

This is to let you know about a research project based on a novel idea of how MS develops. I am a pathologist, and have spent most of my career on medical research. I am returning to researching on MS after a long period of working on the arterial disease that causes heart attacks and strokes. The reason for my return to MS work is that I believe that MS may develop in a way similar to arterial disease when the details of the process, the molecules concerned, are considered. 

Thursday, 16 August 2018

Guest Post: Language and MS: Why Our Words and Stories Matter

Question. Those with multiple sclerosis: do you remember the exact words your neurologist used to break the news of your diagnosis?

Wednesday, 15 August 2018

Neuroinflammation associated with nerve damage in progressive MS

This study looks at neuroinflammation. Specifically the fact that the development of treatments for progressive MS is hampered by the lack of suitable biomarkers that can accurately detect and monitor intrathecal inflammation (inflammation which occurs within the spinal theca, which is a sac containing the cerebrospinal fluid which provides nutrients and buoyancy to the spinal cord).

Tuesday, 14 August 2018

How big is your need to exercise?

The evidence that exercise and I mean regular exercise is good for you is so overwhelming that it is hard to argue against the science. What I mean by this is that almost everyone accepts exercise as being good for the general population and for people with MS. The downside is that some MSers are so disabled and/or have so much fatigue that they find it difficult to exercise. I am prepared to accept the latter, but I am not prepared to accept this as a reason not to promote/prescribe exercise to the wider MS community. The question I have 'Is how do we get MSers and healthcare professionals (HCPs) to exercise regularly?'




Are you interested in hearing more about what you can do?

My Tibetan Odyssey: In search of Gods in the highest of places



Mountain climbing as an obsession is a selfish endeavor, and there’s just no way to get around that fact
       -Beck Weathers in ‘Left for Dead' on the 1996 Everest disaster.

Monday, 13 August 2018

ProfG on Twitter

You may have realized that the number of posts have dropped to one a day. 

Some people felt that the haphazard way the posts were done was over-loading people. What do you think?

Anyway, you may want to know that ProfG has been tweeting his views, notably on papers, rather than blogging them.  

@GavinGiovannoni 

Do you want sound bites or words of wisdom?
6 hours ago

The consequences of Britain's heatwave for MSers is profound

How are you tolerating the heat? One patient after another in my MS clinic yesterday complained about heat sensitivity, worsening fatigue, pseudo-relapses (heat-induced intermittent symptoms) and difficulty sleeping. How are you coping; do you have any advice for your fellow MSers?

London feeling the effects of global warming.

Sunday, 12 August 2018

Friday, 10 August 2018

Congratulations to Trishna!

The Barts-MS team would like to extend their congratulations to friend of the team, campaigner and ambassador for pwMS, and generally splendid person Trishna Bharadia. Read on to find out more.


Wednesday, 8 August 2018

#ThinkHand - What happened to #ChariotMS ?



Yes, what happened you might ask, and all I can say is: A great deal.

Learning from others CD20 depletion do we need to deplete so often.

Kim SH, Kim Y, Kim G, Park NY, Jang HM, Shin HJ, Hyun JW, Kim HJ. Less frequent rituximab retreatment maintains remission of neuromyelitis optica spectrum disorder, following long-term rituximab treatment. J Neurol Neurosurg Psychiatry. 2018 Jun 21. pii: jnnp-2018-318465

Rituximab, a chimeric monoclonal antibody that selectively targets CD20+ B cells, has exhibited robust efficacy and an acceptable safety profile in neuromyelitis optica spectrum disorder (NMOSD). Previously, we reported that the therapeutic response of B cell depletion varied among 100 patients with NMOSD, which resulted from multiple factors including Fc gamma polymorphism, and that monitoring CD27+ memory B cell appears to improve treatment outcomes via individualised treatment. Our treatment strategy has also proven to effectively prevent relapse at a lower cumulative dose, compared with the fixed maintenance therapy every 6 months. Currently, we have a group of patients with NMOSD who have undergone long-term rituximab treatment for more than 7 years. We found that retreatment interval became significantly prolonged over time when we targeted depletion of memory B cells. Here, we analysed clinical outcomes and changes in B cell reconstitution over time, following long-term repeated rituximab treatment.

What's this got to do with MS, as NMO isn't MS. 


Yep, but both respond to CD20 depletion.

We know that there are antibodies to a number of CNS proteins in NMO , notably to a water channel expressed mainly by astrocytes and to a myelin protein. 

In MS, we know some people have antibodies to nerve proteins, but these are rare.

However in both NMO and MS, the dosing schedule is set at every 6 months. We have shown that this is probably too frequent for some people as in the ocrelizumab phase II extension study there was efficacy despite being on no drug for 18months

Baker D, Marta M, Pryce G, Giovannoni G, Schmierer K.
Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis. EBioMedicine. 2017;16:41-50.

Perhaps Relapses in NMO than MS are more frequent but the authors have shown that if you dose according to memory B cell numbers, then you don't need to dose as frequently and being closer to once a year than once every 6 months

The annualised relapse rate was reduced by 97% and 62% patients became relapse-free after rituximab treatment. Disability improved or stabilised in 98% of patients.

This is likely to be the case with ocrelizumab too so can we learn something from other diseases
 

Tuesday, 7 August 2018

Manipulating endocannabinoids degradation does not lead to good myelin repair

ProfG tweeted "I wonder what the MouseDoctor will have to say about this study? #ResearchSpeak Deregulation of the endocannabinoid system and therapeutic potential of ABHD6 blockade in the cuprizone model of demyelination. https://buff.ly/2vjBmRE "

Monday, 6 August 2018

Was George Wrong? Relapse Matter

When CCSVI was in its hayday, the believers would question the immune theory and trot out the suggestion that having relapses didn't matter.

Perhaps not surprising it they had read the Work from The George Ebers Lab

Sunday, 5 August 2018

Daclizumab, The Final Nail

If the answer was daclizumab, I often wondered "What was the question"
I guess we don't need to contemplate this anymore

Friday, 3 August 2018

Oral Cladribine works better than Beta Interferon

Cladribine inhibts MS, as was shown in the CLARITY trials, but it was also indicated in other trials.

The ORACLE trial was at the first demyelinating event, and the ONWARD trial was comparing cladribine with interferon beta. 

These trials were terminated when the manufacturers decided to can the development of oral cladribine.

Guess what the ONWARD trial showed?

Thursday, 2 August 2018

Antibody-mediated autoimmunity in humans

Is MS an autoimmune disease? I don't definitively know.
Is there autoimmunity in MS? Absolutely yes.

Why do we know this?

Because if we take autoantibodies found in MS and inject them into the brains of animals with sub clinical disease triggered by T cells,  they cause disease.


Wednesday, 1 August 2018

Guest post - Reducing MS misdiagnosis: The MS Lesion Checklist

It is estimated that 5-13% of patients diagnosed with MS do not have MS (Solomon et al, Curr Neurol Neurosci Rep, 2013). As MS prevalence in the US may be as high as 208/100,000 persons (Wallin et al, 2017), this would translate into almost 700,000 cases of MS, of whom as many as 70,000 could be misdiagnosed. 

Q & A August



If you have a question unrelated to the thread this is the place for you