Role of cerebral hypoperfusion

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Petr75
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Role of cerebral hypoperfusion

Post by Petr75 » Tue Apr 23, 2019 10:58 am

2019 Mar 14
Department of Neurology, Universitair Ziekenhuis, Brussel
Role of cerebral hypoperfusion in multiple sclerosis (ROCHIMS): study protocol for a proof-of-concept randomized controlled trial with bosentan.
PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416892/

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.

TRIAL REGISTRATION:
Clinical Trials Register, EudraCT 2017-001253-13 . Registered on 15 February 2018.
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WIKI- Bosentan https://en.wikipedia.org/wiki/Bosentan

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Petr75
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Posts: 421
Joined: Sat Oct 19, 2013 10:17 am
Location: Czech Republic

Re: Role of cerebral hypoperfusion

Post by Petr75 » Thu Apr 25, 2019 3:59 am

2019 Jan-Apr
Neuropsychology Section, Departments of Neurology and Psychiatry, University Hospital of Patras and University of Patras Medical School, Patra, Greece
Robust regional cerebral blood flow perfusion deficits in relapsing-remitting multiple sclerosis patients with executive function impairment
https://www.ncbi.nlm.nih.gov/pubmed/30877732

Abstract
OBJECTIVES:
Cognitive impairment is present in up to 65% of Relapsing Remitting Multiple sclerosis (RRMS) patients and can be extremely debilitating. Although deficits in episodic memory and processing speed occur more frequently than executive deficits, executive dysfunction tends to have a significant impact on MS patients' ability to generate strategies, think divergently, solve and estimate problems, and reason in abstract terms with substantial negative impacts on activities of daily living. In the present study we investigated perfusion detection rate and pattern, as well as the association between perfusion rates and cognitive dysfunction in cognitively impaired RRMS patients.
METHODS:
We present findings from 17 cognitively impaired RRMS patients who were evaluated with a comprehensive neuropsychological battery and additionally evaluated by brain perfusion radiopharmaceutical technetium-99m hexamethyl-propylene amine oxime (99mTc HMPAO).
RESULTS:
RRMS patients had hypoperfusion in several predefined Brodmann areas and lobes of the brain, relatively to demographically matched healthy controls according to an established normative database NeuroGam™. However, we noted blood flow reduction, mainly in the frontal lobes and other related prefrontal areas, involving both hemispheres, but with asymmetric left hemisphere predominance. Moreover, associations between measures of response inhibition, set shifting (executive functions) and severity of hypoperfusion in the left frontal lobes were also established.
CONCLUSION:
Cerebral hypoperfusion is an integral feature of MS pathology. Executive dysfunction is associated with robust cerebral perfusion deficits in the frontal and prefrontal cortex of cognitively impaired RRMS patients.

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