Phenylephrine alteration of cerebral blood flow during orthostasis: effect on n-back performance in chronic fatigue syndrome

Abstract

Chronic fatigue syndrome (CFS) with orthostatic intolerance is characterized by neurocognitive deficits and impaired working memory, concentration, and information processing. In CFS, upright tilting [head-up tilt (HUT)] caused decreased cerebral blood flow velocity (CBFv) related to hyperventilation/hypocapnia and impaired cerebral autoregulation; increasing orthostatic stress resulted in decreased neurocognition. We loaded the baroreflex with phenylephrine to prevent hyperventilation and performed n-back neurocognition testing in 11 control subjects and 15 CFS patients. HUT caused a significant increase in heart rate (109.4 ± 3.9 vs. 77.2 ± 1.6 beats/min, P < 0.05) and respiratory rate (20.9 ± 1.7 vs. 14.2 ± 1.2 breaths/min, P < 0.05) and decrease in end-tidal CO2 (ETCO2; 42.8 ± 1.2 vs. 33.9 ± 1.1 Torr, P < 0.05) in CFS vs. control. HUT caused CBFv to decrease 8.7% in control subjects but fell 22.5% in CFS. In CFS, phenylephrine prevented the HUT-induced hyperventilation/hypocapnia and the significant drop in CBFv with HUT (-8.1% vs. -22.5% untreated). There was no difference in control subject n-back normalized response time (nRT) comparing supine to HUT (106.1 ± 6.9 vs. 97.6 ± 7.1 ms at n = 4), and no difference comparing control to CFS while supine (97.1 ± 7.1 vs 96.5 ± 3.9 ms at n = 4). However, HUT of CFS subjects caused a significant increase in nRT (148.0 ± 9.3 vs. 96.4 ± 6.0 ms at n = 4) compared with supine. Phenylephrine significantly reduced the HUT-induced increase in nRT in CFS to levels similar to supine (114.6 ± 7.1 vs. 114.6 ± 9.3 ms at n = 4). Compared with control subjects, CFS subjects are more sensitive both to orthostatic challenge and to baroreflex/chemoreflex-mediated interventions. Increasing blood pressure with phenylephrine can alter CBFv. In CFS subjects, mitigation of the HUT-induced CBFv decrease with phenylephrine has a beneficial effect on n-back outcome.

Dynamic cerebral autoregulation is impaired in Veterans with Gulf War Illness: A case-control study

“…Our recent work demonstrating that cholinergic enhancement was only effective in improving CBF in healthy subjects when upright highlights the importance of orthostatic stress in considering CBF response [ 16 ]. Further support for the importance of orthostatic stress comes from work in chronic fatigue syndrome in which patients not only demonstrated greater drops in CBFV during head up tilt but also impaired cognitive performance when upright but not supine [ 59 ]. Since cognitive complaints in Veterans with GWI are made when they are upright, we must consider the importance of studying the upright posture.…”

Cognitive Function Declines Following Orthostatic Stress in Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

“…Slowed information processing is the most commonly reported objective neurocognitive symptom in ME/CFS patients ( Institute of Medicine [IOM], 2015 ; Mahurin et al, 2004 ; Claypoole et al, 2007 ; Togo et al, 2015 ). As the N-back test is dependent on processing information speed in the working memory, the test has been used to measure cognitive function in ME/CFS patient groups ( Owen et al, 2005 ; Cockshell and Mathias, 2010 ; Stewart et al, 2012 ; Medow et al, 2014 ).…”

Analyzing the neuropsychological characteristics and changes in serum markers of patients with chronic cerebral circulation insufficiency

“…When it decreases to a certain threshold value, the local perfusion will also decrease, causing clinical manifestations such as dizziness and head heaviness, which are usually considered to be the early manifestations of cerebral infarction. [9][10][11][12] As there is no specific manifestation for CCCI clinical symptoms and imaging characteristics, early accurate diagnosis is one of the difficulties in the treatment of this disease. Currently, domestic and foreign studies show that the early manifestations of many patients with chronic cerebral functional insufficiency are experiencing an increase in memory loss and emotional disorders, which is similar to neurosis such as depression and accompanied by mild cognitive disor-der.…”