Tuesday, 17 November 2015

Measuring brain hypoxia in MS

Sci Rep. 2015 Nov 13;5:16477. doi: 10.1038/srep16477.

Reduced cortical microvascular oxygenation in multiple sclerosis: a blinded, case-controlled study using a novel quantitative near-infrared spectroscopy method.

Abstract

Hypoxia (low oxygen) is associated with many brain disorders as well as inflammation, but the lack of widely available technology has limited our ability to study hypoxia in human brain. Multiple sclerosis (MS) is a poorly understood neurological disease with a significant inflammatory component which may cause hypoxia. We hypothesized that if hypoxia were to occur, there should be reduced microvascular hemoglobin saturation (StO2). In this study, we aimed to determine if reduced StO2 can be detected in MS using frequency domain near-infrared spectroscopy (fdNIRS). We measured fdNIRS data in cortex and assessed disability of 3 clinical isolated syndrome (CIS), 72 MS patients and 12 controls. Control StO2 was 63.5 ± 3% (mean ± SD). In MS patients, 42% of StO2 values were more than 2 × SD lower than the control mean. There was a significant relationship between StO2 and clinical disability. A reduced microvascular StO2 is supportive (although not conclusive) that there may be hypoxic regions in MS brain. This is the first study showing how quantitative NIRS can be used to detect reduced StO2 in patients with MS, opening the door to understanding how microvascular oxygenation impacts neurological conditions.

Figure: Measurement of brain oxygenation showing hypoxia in MS, in particular in RRMS [R] with EDSS>3 (moderate disability) and secondary progressive MS [SP]. The green shaded area represents 2 x standard deviation around the control levels.

Using infra-red spectroscopy the authors have quantified the oxygen saturation of RBCs (also called oxyhaemoglobin) in blood vessels supplying the brain grey matter region. Their data suggests that hypoxia (reduced oxygen saturation) exacerbates brain inflammation, leading to greater disease activity (R>3).

However, low levels of oxygen saturation did not directly lead to significant levels of brain atrophy, but did correlate with longer disease duration and increasing levels of disability; suggesting a paradoxical relationship between inflammation, neurodegeneration and disability levels. The reason for the paradox may be that inflammation is more closely linked to motor disability than to a global disease process per se, at least in the grey matter.

Whatever the truth of the matter, there are rarer indications for hyperbaric therapy than MS relapse.

18 comments:

  1. Interesting methodology; this reminds of a "finger clip" for oxygen saturation measurements. Ratiometric measurements would give a more accurate value of oxygen saturation, is it feasible to try quantitative ratiometric measurements in the brain? In any event, if oxygen saturation is ca. 40-60%, no hyperbaric therapy is needed, one can reach higher oxygen saturation at 1 atm (if needed, this can be 1 atm of oxygen).

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    1. The finger clip is usually a pulse oximeter which measures arterial ( big vessel) oxyhemoglobin saturation. This doesn't tend to change much in MS. NIRS looks at the tiny microvessels closer to where gas exchange occurs.

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    2. Dr. Duff, thank you for commenting. The problem I see with NIRS is low intensity of oxyhemoglobin absorption band at ca. 750 nm, and an even lower (close to zero( absorbance of deoxyhemoglobin in this spectral window. The "finger clip" takes advantage of intense visible bands of oxy- and deoxy hemoglobin, which are shifted with respect to each other. One can pick a wavelength where both forms absorb equally (an isosbestic point), and use this point as an "internal standard". Does this approach work in NIRS?

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  2. I did wonder about hypoxia in MS and also if it connects with sleep apnoea. I suffered from sleep apnoea quite a few times before my first MS relapse and during my first relapse. I do quite a bit of stress management daily and the sleep apnoea has stopped for now.

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  3. This proves CCSVI was true all along/

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    1. Anon at 5.32pm - I really hope you are joking! Micro means "very tiny", and everything I've seen about CCSVI relates to veins which are big enough to stretch surgically or put stents into. I can't see that happening with micro vessels

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    2. Only a matter of time before that spurious association was made.

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    3. Yes I was joking which is why I added the slash.

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  4. It's interesting that you mention OSA. There's work in Parkinson's suggesting that it can lead to oxidative stress and brain inflammation.

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    1. I thought this was interesting
      Sleep. 2015 Mar 1;38(3):361-70. doi: 10.5665/sleep.4490.

      White matter damage and systemic inflammation in obstructive sleep apnea.

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    2. Here's the link.
      http://www.ncbi.nlm.nih.gov/pubmed/25325459

      CONCLUSIONS:

      Obstructive sleep apnea impairs white matter integrity in vulnerable regions, and this impairment is associated with increased disease severity. The possible interactions between systemic inflammation and central nervous system microstructural damage may represent variant hypoxic patterns and their consequent processes in OSA.

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    3. Around 30% of PwMS suffer from OSA, more research evidently needs to be done in this area.

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    4. Thanks for your reply. Nocturnal hypoventilation in MS may be worth looking into too perhaps.

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    5. My mother was telling me as a baby my breathing was shallow, I would sleep silently and very still and she would have to touch me to check I was alive. May be it's a trait.

      Congenital central hypoventilation syndrome (CCHS), also known as the Ondine curse, is a rare neurological disorder characterized by inadequate breathing during sleep and, in more severely affected individuals, also during waking periods.

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  5. I got to use a pulse oximeter, or finger better to measure the saturation during physical therapy and the period that did pilates. As I went back to working out at the gym usually soon after the outbreak of the recovery already thought about buying an oximeter for me, because this issue of oxidative stress ...

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  6. The practice of Qigong and Yoga increase oxygen availability and I would be interested to see research how these help MS.

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