Tuesday, 13 January 2015

Predicting progression

Hexosylceramides as intrathecal markers of worsening disability in multiple sclerosis.

Checa A, Khademi M, Sar DG, Haeggström JZ, Lundberg JO, Piehl F, Olsson T, Wheelock CE.
Mult Scler. 2014 . pii: 1352458514561908. [Epub ahead of print]


BACKGROUND:Sphingolipids are important components of neurons and the myelin sheath whose levels are altered in multiple sclerosis (MS).

OBJECTIVES:We aimed to determine if cerebrospinal fluid (CSF) sphingolipids can be used as markers of MS disease progression.

METHODS: We analysed sphingolipids in CSF from 134 individuals. The MS group included 65 patients divided into 41 relapsing-remitting MS (RRMS) and 24 progressive MS (ProgMS). In addition, a group of 13 early MS/clinically isolated syndrome (EarlyMS) and two control groups consisting of 38 individuals with other neurological diseases (OND) and 18 OND with signs of inflammation (iOND) were analysed. A follow-up study included 17 additional RRMS patients sampled at two time points 4.7±1.7 years apart.


RESULTS: Levels of sphingomyelin (SM)- and hexosylceramide (HexCer)-derived sphingolipids increased in the CSF of patients with MS independently of the fatty acid chain length in RRMS (p<0.05). Levels of palmitic acid (16:0)-containing HexCer (HexCer16:0) increased significantly in ProgMS compared with the OND (p<0.001), iOND (p<0.05) and EarlyMS (p<0.01) groups and correlated with Expanded Disability Status Scale in RRMS in both studies (p=0.048; p=0.027).


CONCLUSION:HexCer16:0 is a promising candidate marker of disease progression in MS, especially in RRMS.



Electronmicrograph of whorls of myelin sheath wrapping around an axon

The 16-carbon fatty acid palmitic acid (HexCer 16:0) and other lipids are major components of myelin and form compact, highly organized membrane structures which is important for its role as an electrical insulator of axons. It is therefore not surprising that myelin injury leads to release of fatty acids into the surrounding cerebrospinal fluid, where it is readily measurable. Here the authors demonstrate that release of HexCer 16:0 is a factor associated with progression in MS, in the same way release of neurofilaments from axons is predictive of progression. In another words demyelination causes disability.

Unfortunately, dietary ingestion of fatty acids does not lead to their replacement or incorporation into the brain. Although, subcutaneous injection in mice seems to do the trick!

4 comments:

  1. Alot of my MS progression I can see has been from relapses triggered by infection, trauma to my spine when I already have spine lesions, stress, anxiety, bad posture and lack of exercise, damage from side effects of oral steroids. Pseudo relapses (by infection) I feel have done quite a bit of damage. So that makes me think some of this progression is managable and avoidable.

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    1. Agree with a lot of your own conclusions, although not with the steroids (except their negative impact on bone health and the endocrine system over prolonged use) - as steroids have been shown to improve disability. The key is to recognise relapses early and treat them, then follow this up with physiotherapy/activity to improve the recovery. Although, not everyone is able to accurately assess a relapse and is a sensory relapse less important than a motor relapse - whilst this is all happening we're missing the opportunity to treat it.

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    2. One thing I really can't understand is why i've never been warned about anxiety and stress by any neurologist, GP or MS nurse. Now I know that both these are very unsettling to the CNS it is a surprise. I was reading about stress can cause anxiety and it menioned this is because of the immune system. My GP said to me doctors often don't ask patients the cause/ reason of their stress. But if they were to ask this then it would make the patient aware of their stress, then do something about it.
      I had a bad relapse triggered by stress and anxiety. I have written a list of all the things I was stressed and anxious about before that relapse happened. The list has 12 different stressors. Some are related to each other. One stressor was having the symptoms as I found these stressful and caused me anxiety. I also have read that it's the interplay of the different stressors that is also the problem.

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    3. The reason why I mentioned steroids was because my initial relapse was triggered by an infection, I came to take steroids a month later !! It felt like my body severely reacted to the steroids. I was very stressed and very anxious at the time. I don't know how steroids work but I read something saying they minimic stress. I began five days oral steroids and had a severe relapse starting from that same day or the day after. My immune system and nervous system couldn't cope.

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