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

Abstract

Neurological dysfunction has been reported in Gulf War Illness (GWI), including abnormal cerebral blood flow (CBF) responses to physostigmine challenge. However, it is unclear whether the CBF response to normal physiological challenges and regulation is similarly dysfunctional. The goal of the present study was to evaluate the CBF velocity response to orthostatic stress (i.e., sit-to-stand maneuver) and increased fractional concentration of carbon dioxide. 23 cases of GWI (GWI+) and 9 controls (GWI) volunteered for this study. Primary variables of interest included an index of dynamic autoregulation and cerebrovascular reactivity. Dynamic autoregulation was significantly lower in GWI+ than GWI- both for autoregulatory index (2.99±1.5 vs 4.50±1.5, p = 0.017). In addition, we observed greater decreases in CBF velocity both at the nadir after standing (-18.5±6.0 vs -9.8±4.9%, p = 0.001) and during steady state standing (-5.7±7.1 vs -1.8±3.2%, p = 0.042). In contrast, cerebrovascular reactivity was not different between groups. In our sample of Veterans with GWI, dynamic autoregulation was impaired and consistent with greater cerebral hypoperfusion when standing. This reduced CBF may contribute to cognitive difficulties in these Veterans when upright.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Group-averaged response for sit-to-stand maneuvers.

Physiological responses are averaged across individuals and repeated sit-to-stand maneuvers. From top to bottom, cerebral blood flow velocity (CBFV) expressed as a percentage of rest, mean arterial pressure (MAP) in mmHg, heart rate in beats per minute (BPM), and end-tidal carbon dioxide (CO2) in mmHg averaged second-by-second. Closed and open circles represent cases with (GWI+) and controls (GWI-), respectively. Error bars are standard errors.

Fig 2. Dynamic cerebral autoregulation is impaired in Veterans with Gulf War Illness.

Average autoregulatory indices were computed for three sit-to-stand maneuvers in cases with Gulf War Illness (GWI+) and controls (GWI-), respectively. Veterans with GWI+ had a significantly lower index than GWI-, consistent with impaired autoregulation.

Fig 3. Transfer function estimates of cerebral autoregulation.

From top to bottom, gain, coherence and phase between mean arterial pressure (mmHg) and cerebral flow velocity (%) over the entire frequency spectrum from the very low frequency (VLF: 0.04–0.07), low frequency (LF: 0.07–0.2 Hz) and high frequency (HF: 0.2–0.5 Hz) bands for cases with Gulf War Illness (GWI+) and controls (GWI-). Filled and open circles represent cases (GWI+) and controls (GWI-), respectively. Data are presented as mean ± SE. *, significant difference between GWI+ and GWI- for Gain only, p

Fig 4. Relationship between cerebral blood flow regulation and baroreflex.

Panel A: Correlation between autoregulatory index and the percent change (Δ) in cerebral blood flow velocity (CBFV) during steady state standing (30–55 sec following stand) relative to sitting ([((Standing CBFV – Sitting CBFV)/Sitting CBFV)*100]). Panel B: Correlation between low frequency (LF: 0.04–0.15 Hz) baroreflex sensitivity gain derived from transfer function estimate and the percent decrease in CBFV during nadir (5 beat average), ([((Standing CBFV @ Nadir – Sitting CBFV)/Sitting CBFV)*100]). Filled and open circles represent cases (GWI+) and controls (GWI-), respectively. Regression lines are plotted using all data, and associated R2 values were significant (p<0.05).