Postural neurocognitive and neuronal activated cerebral blood flow deficits in young chronic fatigue syndrome patients with postural tachycardia syndrome

Abstract

Neurocognition is impaired in chronic fatigue syndrome (CFS). We propose that the impairment relates to postural cerebral hemodynamics. Twenty-five CFS subjects and twenty control subjects underwent incremental upright tilt at 0, 15, 30, 45, 60, and 75° with continuous measurement of arterial blood pressure and cerebral blood flow velocity (CBFV). We used an n-back task with n ranging from 0 to 4 (increased n = increased task difficulty) to test working memory and information processing. We measured n-back outcomes by the number of correct answers and by reaction time. We measured CBFV, critical closing pressure (CCP), and CBFV altered by neuronal activity (activated CBFV) during each n value and every tilt angle using transcranial Doppler ultrasound. N-back outcome in control subjects decreased with n valve but was independent of tilt angle. N-back outcome in CFS subjects decreased with n value but deteriorated as orthostasis progressed. Absolute mean CBFV was slightly less than in control subjects in CFS subject at each angle. Activated CBFV in control subjects was independent of tilt angle and increased with n value. In contrast, activated CBFV averaged 0 in CFS subjects, decreased with angle, and was less than in control subjects. CCP was increased in CFS subjects, suggesting increased vasomotor tone and decreased metabolic control of CBFV. CCP did not change with orthostasis in CFS subjects but decreased monotonically in control subjects, consistent with vasodilation as compensation for the orthostatic reduction of cerebral perfusion pressure. Increasing orthostatic stress impairs neurocognition in CFS subjects. CBFV activation, normally tightly linked to cognitive neuronal activity, is unrelated to cognitive performance in CFS subjects; the increased CCP and vasomotor tone may indicate an uncoupling of the neurovascular unit during orthostasis.

Figures

Fig. 1.

Changes in cerebral blood flow velocity (CBFV; top) during the sequence of n-back tasks (n = 0 to 4; bottom). The n-back responses were to alphabetic characters (consonants only) encoded as numbers 2 (= letter “B”) through 26 (= letter “Z”). Randomized n-back sequences were repeated at each angle of tilt. Changes in CBFV were obtained by linear least-squares fits to the data (expressed in units of cm·s−1·min−1). Slopes were subsequently normalized to CBFV for purposes of comparison.

Fig. 2.

Computation of the two-parameter fit using phasic arterial pressure (AP; top) and the corresponding phasic CBFV (middle). Bottom: fits used to obtain the critical closing pressure (CCP; y-intercept) and the resistance-area product (slope).

Fig. 3.

CBFV as a function of tilt angle during incremental upright tilt. Solid lines show data from control subjects; shaded lines show data from chronic fatigue syndrome (CFS)/postural tachycardia syndrome (POTS) subjects. CFS/POTS patients had significantly decreased CBFV by repeated-measures ANOVA. There were, however, no differences in changes of CBFV at any angle.

Fig. 4.

Heart rate [in beats/min (bpm); top] and pulse pressure (bottom) as a function of tilt angle during incremental upright tilt. Solid lines show data from control subjects; shaded lines show data from CFS/POTS subjects. CFS/POTS patients had significantly increased heart rates by repeated-measures ANOVA. Post hoc heart rates at each tilt angle were also different.

Fig. 5.

N-back outcome measures during orthostasis. Top: numbers of correct responses. Bottom: reaction times (in ms). Data are plotted as a function of the incremental tilt angle, which is the repeated-measure factor for each n value. Solid lines show data from control subjects; shaded lines show data from CFS/POTS subjects. Control outcomes worsened (decreased number of correct responses and increased reaction times) with n value but were unaffected by tilt angle. CFS/POTS outcomes were inferior to control outcomes and deteriorated progressively with tilt angle.

Fig. 6.

Cognitive activated mean CBFV during orthostasis. Activated blood flow was measured by the following equation: slope = change in CBFV per minute during n-back. Data are plotted as a function of the incremental tilt angle, which is the repeated-measure factor for each n value. Solid lines show data from control subjects; shaded lines show data from CFS/POTS subjects. Control slopes increased with n value but were unaffected by tilt angle. CFS/POTS slopes statistically increased with n value, deteriorated progressively with tilt angle, and were often <0, signifying a decrease in CBFV in the middle cerebral artery.

Fig. 7.

Resistance-area product (top), Gosling pulsatility index (middle), and CCP (bottom) during orthostasis. Data are plotted as a function of the incremental tilt angle, which is the repeated-measure factor for each n value. Results were independent of n value for all subjects. Solid lines show data from control subjects; shaded lines show data from CFS/POTS subjects. The control resistance-area product was unaffected by tilt angle but increased in CFS/POTS subjects. The control pulsatility index was unaffected by tilt angle but decreased in CFS/POTS subjects. CCP decreased with tilt angle in control subjects. CCP was increased above control for CFS/POTS subjects and was unaffected by tilt angle.