Brain Damage and Motor Cortex Impairment in Chronic Obstructive Pulmonary Disease: Implication of Nonrapid Eye Movement Sleep Desaturation

Abstract

Study objectives: Nonrapid eye movement (NREM) sleep desaturation may cause neuronal damage due to the withdrawal of cerebrovascular reactivity. The current study (1) assessed the prevalence of NREM sleep desaturation in nonhypoxemic patients with chronic obstructive pulmonary disease (COPD) and (2) compared a biological marker of cerebral lesion and neuromuscular function in patients with and without NREM sleep desaturation.

Methods: One hundred fifteen patients with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 2 and 3), resting PaO2 of 60-80 mmHg, aged between 40 and 80 y, and without sleep apnea (apnea-hypopnea index < 15) had polysomnographic sleep recordings. In addition, twenty-nine patients (substudy) were assessed i) for brain impairment by serum S100B (biological marker of cerebral lesion), and ii) for neuromuscular function via motor cortex activation and excitability and maximal voluntary quadriceps strength measurement.

Results: A total of 51.3% patients (n = 59) had NREM sleep desaturation (NREMDes). Serum S100B was higher in the NREMDes patients of the substudy (n = 14): 45.1 [Q1: 37.7, Q3: 62.8] versus 32.9 [Q1: 25.7, Q3: 39.5] pg.ml(-1) (P = 0.028). Motor cortex activation and excitability were lower in NREMDes patients (both P = 0.03), but muscle strength was comparable between groups (P = 0.58).

Conclusions: Over half the nonhypoxemic COPD patients exhibited NREM sleep desaturation associated with higher values of the cerebral lesion biomarker and lower neural drive reaching the quadriceps during maximal voluntary contraction. The lack of muscle strength differences between groups suggests a compensatory mechanism(s). Altogether, the results are consistent with an involvement of NREM sleep desaturation in COPD brain impairment.

Clinical trial registration: The study was registered at www.clinicaltrials.gov as NCT01679782.

Keywords: central nervous system; cerebral cortex; electromyography; muscle weakness; voluntary activation.

Figure 1

Flow diagram of the trial. The patients were assessed for eligibility at the beginning of a 4-w inpatient pulmonary rehabilitation program. All tests were completed within the first week following admission.

Figure 2

Experimental design. Gray rectangles represent voluntary quadriceps contractions at maximal (MVC) or submaximal intensity at 50 and 30% of MVC. Superimposed and control doublets, maximal M-waves (Mmax), and maximal H-waves (Hmax) were delivered via electrical stimulation over the femoral nerve. Motor-evoked potentials (MEP) were delivered over the motor cortex via transcranial magnetic stimulation.

Figure 3

Median and quartiles box plots of serum S100B concentration in the patients with COPD experiencing desaturation (NREMDes) and nondesaturation (NREMnoDes) (non-parametric data). NREM = nonrapid eye movement.

Figure 4

(A) Maximal quadriceps torque (QMVC), quadriceps peak twitch (QPt) and peripheral voluntary activation (peripheral VA) in patients with COPD experiencing desaturation (NREMDes) and nondesaturation (NREMnoDes). (B) Medians and quartile box plots of motor cortex activation (cortical VA) in patients with COPD experiencing desaturation (NREMDes) and nondesaturation (NREMnoDes) (nonparametric data). NREM, nonrapid eye movement.