Role of cerebral hypoperfusion in MS

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.
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frodo
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Role of cerebral hypoperfusion in MS

Post by frodo » Wed Mar 20, 2019 8:33 am

Role of cerebral hypoperfusion in MS. ROCHIMS: study protocol for a proof-of-concept randomized controlled trial with bosentan

https://trialsjournal.biomedcentral.com ... 019-3252-4

Abstract
Background

Axonal degeneration is related to long-term disability in patients with multiple sclerosis (MS). The underlying mechanism remains ill understood but appears to involve axonal energetic dysfunction. A globally impaired cerebral blood flow (CBF) has been observed in the normal-appearing white matter (NAWM) of patients with MS, which is probably related to astrocytic overexpression of endothelin-1 (ET-1). Cerebral hypoperfusion has been associated with reduced mitochondrial activity and disabling symptoms (e.g. fatigue and cognitive decline) of MS. Countering this process could therefore be beneficial in the disease course. Short-term CBF restoration with a single 62.5-mg dose of the ET-1 receptor antagonist bosentan has already been demonstrated in patients with MS.
Methods

The ROCHIMS study is a proof-of-concept double-blind randomized clinical trial in which patients with relapsing-remitting MS will receive either 62.5 mg bosentan or matching placebo twice daily during 28 ± 2 days. Clinical evaluation and brain magnetic resonance imaging (MRI) will be performed at baseline and treatment termination. Based on previous work, we expect a global increase of CBF in the individuals treated with bosentan. The primary outcome measure is the change of N-acetyl aspartate in centrum semiovale NAWM, which is a marker of regional axonal mitochondrial activity. Other parameters of interest include changes in fatigue, cognition, motor function, depression, and brain volume.
Discussion

We hypothesize that restoring cerebral hypoperfusion in MS patients improves axonal metabolism.

Early positive effects on fatigue and cognitive dysfunction related to MS might additionally be detected. There is a medical need for drugs that can slow down the progressive axonal degeneration in MS, making this an important topic of interest.

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NHE
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Re: Role of cerebral hypoperfusion in MS

Post by NHE » Thu Mar 21, 2019 12:30 pm

frodo wrote:
Wed Mar 20, 2019 8:33 am
Role of cerebral hypoperfusion in MS. ROCHIMS: study protocol for a proof-of-concept randomized controlled trial with bosentan

https://trialsjournal.biomedcentral.com ... 019-3252-4

-----------------------------------------------------------------------------

The ROCHIMS study is a proof-of-concept double-blind randomized clinical trial in which patients with relapsing-remitting MS will receive either 62.5 mg bosentan or matching placebo twice daily during 28 ± 2 days.
Bosentan is a fairly toxic drug. It is only available under an FDA-mandated risk evaluation and mitigation strategy (REMS) with respect to risks to fetuses and its risks of causing liver damage.

It also carries a risk of other rather deleterious side effects.

https://www.mayoclinic.org/drugs-supple ... g-20068086

  • Blurred vision
    confusion
    dizziness
    dark urine
    faintness or lightheadedness when getting up from a lying or sitting position
    fever with or without chills
    light-colored stools
    loss of appetite
    nausea
    stomach pain
    sudden sweating
    unusual tiredness or weakness
    vomiting
    yellow eyes or skin

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CureOrBust
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Re: Role of cerebral hypoperfusion in MS

Post by CureOrBust » Thu Mar 28, 2019 4:49 pm

Although the drug they tested sounds like a risky option in itself, what I do see (in the half full cup) is an opportunity to better understand the disease, and what may improve matters, by the way the drug causes its effects.

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NHE
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Re: Role of cerebral hypoperfusion in MS

Post by NHE » Thu Mar 28, 2019 11:29 pm

CureOrBust wrote:
Thu Mar 28, 2019 4:49 pm
Although the drug they tested sounds like a risky option in itself, what I do see (in the half full cup) is an opportunity to better understand the disease, and what may improve matters, by the way the drug causes its effects.
Ginkgo may be an alternative option.

Reversing brain damage in former NFL players: implications for traumatic brain injury and substance abuse rehabilitation.
https://www.ncbi.nlm.nih.gov/pubmed/21615001

Effects of Ginkgo biloba on cerebral blood flow assessed by quantitative MR perfusion imaging: a pilot study.
https://www.ncbi.nlm.nih.gov/pubmed/21061003

Cognitive performance, SPECT, and blood viscosity in elderly non-demented people using Ginkgo biloba.
https://www.ncbi.nlm.nih.gov/pubmed/12905098

The effect of Ginkgo biloba on functional measures in multiple sclerosis: a pilot randomized controlled trial.
https://www.ncbi.nlm.nih.gov/pubmed/16781604

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NHE
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Re: Role of cerebral hypoperfusion in MS

Post by NHE » Fri Mar 29, 2019 11:49 pm

PQQ might also be helpful.

Effects of Antioxidant Supplements (BioPQQ™) on Cerebral Blood Flow and Oxygen Metabolism in the Prefrontal Cortex.
Adv Exp Med Biol. 2016;923:215-222.
  • Pyrroloquinoline quinone (PQQ) is a quinone compound originally identified in methanol-utilizing bacteria and is a cofactor for redox enzymes. At the Meeting of the International Society on Oxygen Transport to Tissue (ISOTT) 2014, we reported that PQQ disodium salt (BioPQQ™) improved cognitive function in humans, as assessed by the Stroop test. However, the physiological mechanism of PQQ remains unclear. In the present study, we measured regional cerebral blood flow (rCBF) and oxygen metabolism in prefrontal cortex (PFC), before and after administration of PQQ, using time-resolved near-infrared spectroscopy (tNIRS). A total of 20 healthy subjects between 50 and 70 years of age were administered BioPQQ™ (20 mg) or placebo orally once daily for 12 weeks. Hemoglobin (Hb) concentration and absolute tissue oxygen saturation (SO2) in the bilateral PFC were evaluated under resting conditions using tNIRS. We found that baseline concentrations of hemoglobin and total hemoglobin in the right PFC significantly increased after administration of PQQ (p < 0.05). In addition, decreases in SO2 level in the PFC were more pronounced in the PQQ group than in the placebo group (p < 0.05). These results suggest that PQQ causes increased activity in the right PFC associated with increases in rCBF and oxygen metabolism, resulting in enhanced cognitive function.

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Re: Role of cerebral hypoperfusion in MS

Post by Cece » Thu May 23, 2019 4:45 am

alright, never mind, I am going to take PQQ

I keep thinking what I need to do is exercise more but it is hard to do that consistently!

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