Phrenic nerve involvement and respiratory muscle weakness in patients with Charcot‐Marie‐Tooth disease 1A

Abstract

Diaphragm weakness in Charcot‐Marie‐Tooth disease 1A (CMT1A) is usually associated with severe disease manifestation. This study comprehensively investigated phrenic nerve conductivity, inspiratory and expiratory muscle function in ambulatory CMT1A patients. Nineteen adults with CMT1A (13 females, 47 ± 12 years) underwent spiromanometry, diaphragm ultrasound, and magnetic stimulation of the phrenic nerves and the lower thoracic nerve roots, with recording of diaphragm compound muscle action potentials (dCMAP, n = 15), transdiaphragmatic and gastric pressures (twPdi and twPgas, n = 12). Diaphragm motor evoked potentials (dMEP, n = 15) were recorded following cortical magnetic stimulation. Patients had not been selected for respiratory complaints. Disease severity was assessed using the CMT Neuropathy Scale version 2 (CMT‐NSv2). Healthy control subjects were matched for age, sex, and body mass index. The following parameters were significantly lower in CMT1A patients than in controls (all P < .05): forced vital capacity (91 ± 16 vs 110 ± 15% predicted), maximum inspiratory pressure (68 ± 22 vs 88 ± 29 cmH2O), maximum expiratory pressure (91 ± 23 vs 123 ± 24 cmH2O), and peak cough flow (377 ± 135 vs 492 ± 130 L/min). In CMT1A patients, dMEP and dCMAP were delayed. Patients vs controls showed lower diaphragm excursion (5 ± 2 vs 8 ± 2 cm), diaphragm thickening ratio (DTR, 1.9 [1.6‐2.2] vs 2.5 [2.1‐3.1]), and twPdi (8 ± 6 vs 19 ± 7 cmH2O; all P < .05). DTR inversely correlated with the CMT‐NSv2 score (r = −.59, P = .02). There was no group difference in twPgas following abdominal muscle stimulation. Ambulatory CMT1A patients may show phrenic nerve involvement and reduced respiratory muscle strength. Respiratory muscle weakness can be attributed to diaphragm dysfunction alone. It relates to neurological impairment and likely reflects a disease continuum.

Evaluation of Respiratory Muscle Strength and Diaphragm Ultrasound: Normative Values, Theoretical Considerations, and Practical Recommendations

“…Discrimination of the pleural and peritoneal layers in these patient groups may also be more challenging than in healthy volunteers as some patients suffer from malnutrition and hypoalbunemia, possibly leading to anasarca. However, several studies have proven that diaphragm thickness can exactly be determined not only in healthy subjects but also in neuromuscular disease patients in whom these problems are not present [31][32][33][34][35][36]. Finally, we did not specifically measure SNIP in our study cohort.…”

Genetic Neuropathy Due to Impairments in Mitochondrial Dynamics

“…and the involvement of other organ systems may also occur [31,32]. Furthermore, the neurological deficits from HMSN also result in the secondary involvement of other systems, most commonly the skeletal system (for example, scoliosis [33] and orthopaedic injuries to the feet and ankles [34]) and respiratory system (due to phrenic nerve involvement [35], vocal cord paresis [36], or above-mentioned scoliosis).…”

Long‐term walking ability and patient satisfaction after lower limb functional surgery in patients affected by Charcot‐Marie‐Tooth disease: A retrospective study

“…In the sample, pGCI median score was 5, with a distribution ranging between 1 and 7, as shown in Figure 3. Noteworthy, nearly 80% of the sample patients either improved 4,5 or displayed a considerable improvement. 6,7 Six out of seven patients with pGIC <3 had a WHS score ≥4.…”

“…4 The disease is degenerative and usually shows a slow progression, involving the hands and the respiratory functions, consequently decreasing the patient's quality of life significantly. 5,6 Pharmacological treatments are under investigations; however, as of today, only the rehabilitative management of the disease seems to be of any real use. This includes physiotherapy to maintain joint mobility, to increase muscle strength, and to improve both postural control and endurance; the use of orthoses to enhance walking efficiency, and foot functional surgery (FS) to correct ankle deformities and to improve gait functionality.…”