Sweetman Hannah, Rahman Mahmudur, Vedantam Aditya, Satkunendrarajah Kajana
Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA; Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI, USA.
Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA.
Exp Neurol. 2024 Jan;371:114600. doi: 10.1016/j.expneurol.2023.114600. Epub 2023 Oct 29.
Degenerative cervical myelopathy (DCM) is a debilitating neurological condition characterized by chronic compression of the cervical spinal cord leading to impaired upper and lower limb function. Despite damage to areas of the cervical spinal cord that house the respiratory network, respiratory dysfunction is not a common symptom of DCM. However, DCM may be associated with respiratory dysfunction, and this can affect the ventilatory response to respiratory challenges during emergence from anesthesia, exercise, or pulmonary disease. Surgical spinal cord decompression, which is the primary treatment for DCM, leads to improved sensorimotor function in DCM; yet its impact on respiratory function is unknown. Here, using a clinically relevant model of DCM, we evaluate respiratory function during disease progression and assess adaptive ventilation to hypercapnic challenge before and after surgical intervention. We show that despite significant and progressive forelimb and locomotor deficits, there was no significant decline in eupneic ventilation from the early to late phases of spinal cord compression. Additionally, for the first time, we demonstrate that despite normal ventilation under resting conditions, DCM impairs acute adaptive ventilatory ability in response to hypercapnia. Remarkably, akin to DCM patients, surgical decompression treatment improved sensorimotor function in a subset of mice. In contrast, none of the mice that underwent surgical decompression recovered their ability to respond to hypercapnic ventilatory challenge. These findings underscore the impact of chronic spinal cord compression on respiratory function, highlighting the challenges associated with ventilatory response to respiratory challenges in individuals with DCM. This research highlights the impact of cervical spinal cord compression on respiratory dysfunction in DCM, as well as the persistence of adaptive ventilatory dysfunction after surgical spinal cord decompression. These results indicate the need for additional interventions to enhance recovery of respiratory function after surgery for DCM.
退行性颈椎脊髓病(DCM)是一种使人衰弱的神经系统疾病,其特征是颈椎脊髓长期受压,导致上肢和下肢功能受损。尽管容纳呼吸网络的颈髓区域受到损伤,但呼吸功能障碍并非DCM的常见症状。然而,DCM可能与呼吸功能障碍有关,这会影响麻醉苏醒、运动或肺部疾病期间对呼吸挑战的通气反应。脊髓减压手术是DCM的主要治疗方法,可改善DCM患者的感觉运动功能;但其对呼吸功能的影响尚不清楚。在此,我们使用与临床相关的DCM模型,评估疾病进展过程中的呼吸功能,并评估手术干预前后对高碳酸血症挑战的适应性通气。我们发现,尽管存在明显且逐渐加重的前肢和运动功能缺陷,但从脊髓受压的早期到晚期,平静通气并无显著下降。此外,我们首次证明,尽管在静息状态下通气正常,但DCM会损害对高碳酸血症的急性适应性通气能力。值得注意的是,与DCM患者类似,手术减压治疗改善了一部分小鼠的感觉运动功能。相比之下,接受手术减压的小鼠均未恢复对高碳酸血症通气挑战的反应能力。这些发现强调了慢性脊髓受压对呼吸功能的影响,突出了DCM患者在应对呼吸挑战时通气反应所面临的挑战。这项研究强调了颈髓受压对DCM呼吸功能障碍的影响,以及脊髓减压手术后适应性通气功能障碍的持续存在。这些结果表明,需要采取额外的干预措施来促进DCM手术后呼吸功能的恢复。