Institute of Physiology, Instituto de Medicina Molecular João Lobo Antunes, Centro de Estudos Egas Moniz, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal; Department of Neurosciences and Mental Health, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.
Department of Physical Medicine and Rehabilitation, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.
J Neurol Sci. 2024 May 15;460:123021. doi: 10.1016/j.jns.2024.123021. Epub 2024 Apr 18.
Late-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa treatment. This suggest that other pathophysiological mechanisms than muscle fibre lesion can contribute to the respiratory failure process. We investigate through neurophysiology whether spinal phrenic motor neuron dysfunction could contribute to diaphragm weakness in LOPD patients.
A group of symptomatic LOPD patients were prospectively studied in our centre from January 2022 to April 2023. We collected both demographic and clinical data, as well as neurophysiological parameters. Phrenic nerve conduction studies and needle EMG sampling of the diaphragm were perfomed.
Eight treated LOPD patients (3 males, 37.5%) were investigated. Three patients (37.5%) with no respiratory involvement had normal phrenic nerve motor responses [median phrenic compound muscle action potential (CMAP) amplitude of 0.49 mV; 1st-3rd interquartile range (IQR), 0.48-0.65]. Those with respiratory failure (under nocturnal non-invasive ventilation) had abnormal phrenic nerve motor responses (median phrenic CMAP amplitude of 0 mV; 1st-3rd IQR, 0-0.15), and were then investigated with EMG. Diaphragm needle EMG revealed both myopathic and neurogenic changes in 3 (60%) and myopathic potentials in 1 patient. In the last one, no motor unit potentials could be recruited.
Our study provide new insights regarding respiratory mechanisms in LOPD, suggesting a contribution of spinal phrenic motor neuron dysfunction for diaphragm weakness. If confirmed in further studies, our results recommend the need of new drugs crossing the blood-brain barrier.
尽管定期接受重组人葡糖脑苷脂酶治疗，迟发性庞贝病（LOPD）患者在疾病过程中的某个阶段仍可能需要通气支持。这表明，除了肌肉纤维损伤之外，其他病理生理机制也可能导致呼吸衰竭。我们通过神经生理学研究来探究脊髓膈神经运动神经元功能障碍是否会导致 LOPD 患者的膈肌无力。
从 2022 年 1 月至 2023 年 4 月，我们前瞻性地研究了我们中心的一组有症状的 LOPD 患者。我们收集了人口统计学和临床数据以及神经生理学参数。进行了膈神经传导研究和膈神经针极肌电图采样。
共研究了 8 名接受治疗的 LOPD 患者（3 名男性，37.5%）。3 名（37.5%）无呼吸受累的患者膈神经运动反应正常[膈神经复合肌肉动作电位（CMAP）幅度中位数为 0.49 mV；1 至 3 四分位距（IQR），0.48-0.65]。有呼吸衰竭（接受夜间无创通气）的患者膈神经运动反应异常（膈神经 CMAP 幅度中位数为 0 mV；1 至 3 IQR，0-0.15），随后进行 EMG 检查。3 名患者（60%）的膈肌针极肌电图显示既有肌病性改变又有神经源性改变，1 名患者显示肌病性电位。在最后一名患者中，无法募集运动单位电位。
我们的研究为 LOPD 的呼吸机制提供了新的见解，提示脊髓膈神经运动神经元功能障碍可能导致膈肌无力。如果在进一步的研究中得到证实，我们的结果建议需要新的能够穿过血脑屏障的药物。
