Tuesday, 12 December 2017

Can you eat your way to happiness?

Fitzgerald KC, Tyry T, Salter A, Cofield SS, Cutter G, Fox R, Marrie RA.

Diet quality is associated with disability and symptom severity in multiple sclerosis. 

Neurology. 2017 Dec 6. pii: 10.1212/WNL.0000000000004768.

OBJECTIVE:To assess the association between diet quality and intake of specific foods with disability and symptom severity in people with multiple sclerosis (MS).

METHODS:In 2015, participants in the North American Research Committee on MS (NARCOMS) Registry completed a dietary screener questionnaire that estimates intake of fruits, vegetables and legumes, whole grains, added sugars, and red/processed meats. We constructed an overall diet quality score for each individual based on these food groups; higher scores denoted a healthier diet. We assessed the association between diet quality and disability status as measured using Patient-Determined Disease Steps (PDDS) and symptom severity using proportional odds models, adjusting for age, sex, income, body mass index, smoking status, and disease duration. We assessed whether a composite healthy lifestyle measure, a healthier diet, healthy weight (body mass index <25), routine physical activity, and abstinence from smoking was associated with symptom severity.

RESULTS:Of the 7,639 (68%) responders, 6,989 reported physician-diagnosed MS and provided dietary information. Participants with diet quality scores in the highest quintile had lower levels of disability (PDDS; proportional odds ratio [OR] for Q5 vs Q1 0.80; 95% confidence interval [CI] 0.69-0.93) and lower depression scores (proportional OR for Q5 vs Q1 0.82; 95% CI 0.70-0.97). Individuals reporting a composite healthy lifestyle had lower odds of reporting severe fatigue (0.69; 95% CI 0.59-0.81), depression (0.53; 95% CI 0.43-0.66), pain (0.56; 95% CI 0.48-0.67), or cognitive impairment (0.67; 95% CI 0.55-0.79).

CONCLUSIONS:Our large cross-sectional survey suggests a healthy diet and a composite healthy lifestyle are associated with lesser disability and symptom burden in MS.

"Very little is needed to make a happy life; 
It is all within yourself, in your way of thinking"
-Marcus Aurelius, Roman Emperor

A sobering thought indeed. A chorus of cherubs play accompaniment and pantomime their way across the screen as I write this. Although, enlightening I don't think Marcus Aurelius' philosophy is entirely true.

Let me explain.

We spend most of our lives hanging on for dear life to ideologies and lifestyles, so to speak, to decamp the emotional and physical baggage of a lifetime. The next fad, the next diet; all of which require sustained commitment on our part, but none of which bring us any true level of happiness in the long run...It has taken me a while to realise that durable happiness is an assimilation of the collective camaradrie of those around you. People (plural) need other people (singular/plural) - you matter very much to your partner and your loved ones; the rest as they say is window dressing.

In this article, Fitzgerald et al. tell us that diet quality impacts on disability in MS. They have even gone as far as to define what they think is a composite of a healthy lifestyle: healthy weight (BMI <25), routinely engages in physical activity, abstains from smoking, and consumes a better than average diet (>median diet quality score). Latter was quantified in quintiles as consumption of a) more fruits, vegetables, legumes (fifth quintile=most), b) more whole grains (fifth quintile=most), c) less sugar from desserts and beverages (fifth quintile=least), and d) less red and processed meats (fifth quintile=least).
They have surveyed 11,100 active PwMS in the NARCOMS registry - that is 69% of the registry (responders and nonresponders had similar disability at enrollment). Those with better diet quality scores tended to be less overweight, more likely to partake in physical activity, follow a special diet for MS and less likely to be smokers. They also tended to have lower odds of severe depressive symptoms after adjusting for disability level.

PwMS in the highest quintile vs lowest quintile of diet quality score were at 20% lower risk for severe vs mild self-reported disability (OR 0.77; 95% CI 0.61-0.98), after controlling for age, disease-duration, BMI, income, smoking. Exposure to a weight loss plan diet was associated with lower disability (OR 0.88;m 95% CI 0.79-0.99), however the Wahls diet (adding more leafy green vegetables to your diet) and a gluten free diet was associated with greater disability (Wahls OR 1.51, 95% CI 1.25-1.78 and gluten free OR 1.31, 95% CI 1.13-1.52); although those on the Wahls diet were 50% more likely to have progressive MS and therefore this finding maybe more reflective of this. A greater intake of whole grains and diary, however, were most favourable in the individual food group analyses to have lower odds of severe disability.

Of course, none of this is a causal association for disability in MS, in a nutshell the survey is simply a snapshot of dietary habits of the healthy and not so healthy. Also, surveys as a rule attract a certain demographic and in this case, were more likely to be Caucasian, married and of a higher income.

As a vegetarian, I count myself lucky. I seem to meet the requirements of these surveys even without lifting a finger!

Monday, 11 December 2017

Temperature dependence of impulse conduction in optic nerve axons

Thanks for the comments
We were grateful when a number of readers responded to our enquiry regarding temperature dependent symptoms in MS, and we learned more about how people cope with the symptoms. Following this conversation, I thought it worthwhile to draw attention to a paper we recently published, that suggests that there are functional differences between normal peripheral and central axons, and these differences provide a new view on temperature sensitivity.   

Education: What do antibodies do

You have full text access to this OnlineOpen article
Prospects from systems serology research
Kelly B. Arnold and Amy W. Chung
Version of Record online: 1 DEC 2017 | DOI: 10.1111/imm.12861

An internal cell signalling molecule found to support remyelination

The protein tyrosine phosphatase Shp2 regulates oligodendrocyte differentiation and early myelination and contributes to timely remyelination. Ahrendsen JT, Harlow DE, Finseth LT, Bourne JN, Hickey SP, Gould EA, Culp CM, Macklin WB. J Neurosci. 2017 pii: 2864-16.

Shp2 is a nonreceptor protein tyrosine phosphatase that has been shown to influence neurogenesis, oligodendrogenesis, and oligodendrocyte differentiation. Furthermore, Shp2 is a known regulator of the Akt/mTOR and ERK signaling pathways in multiple cellular contexts, including oligodendrocytes. Its role during later postnatal CNS development or in response to demyelination injury has not been examined. Based on the current studies, we hypothesize that Shp2 is a negative regulator of CNS myelination. Using transgenic mouse technology, we show that Shp2 is involved in oligodendrocyte differentiation and early myelination, but is not necessary for myelin maintenance. We also show that Shp2 regulates the timely differentiation of oligodendrocytes following lysolecithin-induced demyelination, although apparently normal remyelination occurs at a delayed time point. These data suggest that Shp2 is a relevant therapeutic target in demyelinating diseases such as multiple sclerosis.

SIGNIFICANCE STATEMENT In the present study, we show that the protein phosphatase Shp2 is an important mediator of oligodendrocyte differentiation and myelination, both during developmental myelination as well as in myelin regeneration. We provide important insight into the signaling mechanisms regulating myelination and propose that Shp2 acts as a transient brake to the developmental myelination process. Furthermore, we show that Shp2 regulates oligodendrocyte differentiation following demyelination and therefore has important therapeutic implications in diseases such as multiple sclerosis
                                     Expression from Brain seq
Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), SHP-2, or protein-tyrosine phosphatase 2C (PTP-2C) is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. 

This PTP is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as mitogenic activation, metabolic control, transcription regulation, and cell migration. 

Mutations in this gene are a cause of Noonan syndrome and Leopard syndrome as well as acute myeloid leukemia.

Is this going to be a good target for remyelination without side-effects, one would think this will be unlikely as the molecule is expressed at high levels all over the place. 

This feature seems to be common for many of the remyelination .pathways. However do we need to treat long term or give a pulse treatment?

We dont know...becuase we are not testing for this. The models used naturally repair without any treatment so all we are seeing in an enhanced repair. People never look at what happens in a model where there is chronic demyelination yet we jump from these simple models straight into human trials.

Is it surprising that we often struggle to see benefit.

Sunday, 10 December 2017

Measuring Hand Function

Online monitoring of hand function. Are you up for doing the BRAIN test or will the cardboard 9HPT do the job? 

Saturday, 9 December 2017

Relapse without cell depletion in the blood

As you may be aware I have been banging on about the importance of B memory cells for most of the year, but it has been an uphill struggle to get this view accepted. 

However, response to therapy creates a powerful piece of insight that frankly can't be ignored. But I meet Ostriches ever day.

Friday, 8 December 2017

Fingolimod: does it help with upper limb function?

ProfG G has been been saying that we should #Thinkhand and target hand function for outcomes in clinical trials. This idea may be supported by studies with ocrelizumab and natalizumab but there are a couple of exceptions.

Thursday, 7 December 2017

Reflections on the ECF 2017

I have just returned from the European Charcot Foundation meeting in Baveno, Italy. The meeting is small (< 500 attendees) with no parallel sessions and ample time to mix with attendees and chew the cud. I did a plenary presentation on "dealing with increasing economic constraints".  The feedback I received after my talk, and subsequently via email, has been extraordinary. An eminent neurologist said he was glad that someone was thinking about these issues and taking it on. I have also been contacted by a health economist and have been urged to write up the talk.

Wednesday, 6 December 2017

Yet more data supports the B memory Cell idea

I can hear you saying, "Oh no not another B-cell paper!". However, this is where the action is. It is the B-cell and not the T-cell. Do you agree or disagree? Have your say. 

Tuesday, 5 December 2017

Blood cancers after fingolimod treatment

How immunosuppressive is fingolimod? Does fingolimod's longterm immunosuppression result in an increased cancer risk?