Thursday, 3 September 2015

ResearchSpeak: brain plasticity in early MS

Is MS shredding your reserve capacity? #ResearchSpeak #MSBlog

"What protects MSers from noticing cognitive and physical impairments early in the course of their disease are compensatory mechanisms that adjust for the damage that has already accumulated from MS. The ability to compensate is dependent on so called brain, or neuronal, reserve. With increasing damage the reserve capacity gets exhausted and MSers then notice their disabilities and enter the clinically-apparent progressive phase of the disease. Using reserve systems to compensate for damage does come with a downside, characteristically cognitive fatigue."

"The neurophysiological study below shows that MSers are using reserve systems to complete a cognitive task called the auditory oddball task. The oddball task is an experimental design used within event-related potential research (neurophysiology), where presentations of sequences of repetitive auditory stimuli are infrequently interrupted by a deviant stimulus (odd-stimulus). The MSer is asked to react either by counting or by button pressing incidents of target stimuli that are hidden as rare occurrences amongst a series of more common stimuli, that don't require a response. It has been found that an event related electrical activity across the central areas of the brain usually occur around 300 ms and are referred to as the P300 wave (p = positive wave); this positive wave  is larger after the deviant or target stimulus. In the study below the waveform across the brain in MSers differed from normal control subject implying MSers were using different/additional neuronal systems to complete the task; i.e. identify the deviant stimulus."

"Does this research  have relevance to you? Yes, it does. Simply because you 'feel normal' and appear to be 'functioning normally' does not mean to say you have not acquired any damage and long-lasting problems as a result of your MS. In the initial stages of MS the damage accumulates slowly and silently. MS may be gradually chewing-up, or shredding, your reserve capacity. Please note this does not necessarily happen in all MSers; the only way to find out if your MS is active is to be monitored with regular MRI scans. Clinical monitoring is simply not good enough. We know that benign MS does occur, but in untreated populations benign MS is relatively uncommon. What we are trying to do with early effective treatments is to increase the proportion of MSers who turn out to have benign disease. To get this message across and to get people to adopt early effective treatment, with active monitoring, we are launching a policy document at ECTRIMS called 'Brain Health: time matters in MS'. As soon as the document is available I will be sharing it with you."





López-Góngora et al. Neurophysiological Evidence of Compensatory Brain Mechanisms in Early-Stage Multiple Sclerosis. PLoS One. 2015; 10(8):e0136786.

Background: Multiple sclerosis (MS) is a chronic central nervous system disorder characterized by white matter inflammation, demyelination and neurodegeneration. Although cognitive dysfunction is a common manifestation, it may go unnoticed in recently-diagnosed patients. Prior studies suggest MS patients develop compensatory mechanisms potentially involving enhanced performance monitoring. 


Methods: Here we assessed the performance monitoring system in early-stage MS patients using the error-related negativity (ERN), an event-related brain potential (ERP) observed following behavioral errors. Twenty-seven early-stage MS patients and 31 controls were neuropsychologically assessed. Electroencephalography recordings were obtained while participants performed: a) a stop task and b) an auditory oddball task. Behavior and ERP measures were assessed. 

Results: No differences in performance were found between groups in most neuropsychological tests or in behavior or ERP components in the auditory oddball task. However, the amplitude of the ERN associated with stop errors in the stop task was significantly higher in patients. ERN amplitude correlated positively with scores on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and negatively with the time since last relapse. 

Conclusions: Patients showed higher neuronal recruitment in tasks involving performance monitoring. Results suggest the development of compensatory brain mechanisms in early-stage MS and reflect the sensitivity of the ERN to detect these changes.

17 comments:

  1. And with spinal lesions, so characteristic of PPMS, there is practically no reserve.

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  2. Why not also offer neuroprotectants and antioxidants for RRMS in the initial stages? Why only immunosuppressives?

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    1. Sadly, research on neuroprotectives has lagged way behind immunosuppressives up till now, we have been focussing on this for some time now but we need more groups, both research and clinical to be doing the same. All I can say is the pace is accelerating.

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    2. why not.....Evidence. Until it is proven to be of value how do you get the payers to pay for it.
      We are doing such a study and planned another one called DEFLAMES but until the trialz are done there is no evidence.

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    3. why not.....Evidence. Until it is proven to be of value how do you get the payers to pay for it.
      We are doing such a study and planned another one called DEFLAMES but until the trialz are done there is no evidence.

      Delete
  3. Dear MD & MD2,

    What is the difference between a neuroprotective agent and an anti inflammatory agent?

    Thanks,

    -Aidan

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    1. Hi Aidan
      An anti-inflammatory in the case of MS is an agent that stops or reduces the severity of a relapse by acting on the immune system. Stopping inflammation in the brain can itself be neuroprotective as it is stopping an event that is damaging to nerve cells.
      Neuroprotectants are agents that can protect nerve cells from dying as a result of the inflammation and damage accrued after inflammation such as seen in progressive MS where there is less inflammation but the nerves slowly degenerate. Neuroprotectants act on slowing or stopping nerve cell death and are not anti-inflammatory. We need a combination of both for MS in my opinion.

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    2. Which neuroprotectants would you recommend?

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    3. Proven neuroprotectives... I wish... And live in hope.

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    4. There many neuroprotectives we just have to find the best way to detect them. Na channels blockers worked.

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    5. Like this? http://www.ncbi.nlm.nih.gov/pubmed/23518709

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    6. Yes and if I can be forgiven for quoting one of our own http://brain.oxfordjournals.org/content/137/1/92.long

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    7. There many neuroprotectives we just have to find the best way to detect them. Na channels blockers worked.

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  4. Prof G, Why do you think EBV rather JCV maybe is implicated in MS? 90% people maybe has JCV. When a MSers is negative for JCV maybe the test disponible is not necessarily good for search it. I think this because JCV symptoms are very similar MS

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  5. I've had a couple of what my neurologist called "reactivations". It's basically a mild resurfacing of old symptoms for anywhere from a few days to a couple weeks, so they don't consider them actual "relapses" where I've experienced very noticeable new symptoms that took months to resolve. However, my MRI's all look good without any new lesions.

    Is this an example of my reserve capacity being shredded? Or is this just a normal experience because of existing damage?

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