Seong Woong Kang

Assisted Cough and Pulmonary Compliance in Patients with Duchenne Muscular Dystrophy

The aim of this study was to investigate the factors affecting cough ability, and to compare the assisted cough methods in patients with Duchenne muscular dystrophy (DMD). A total seventy-one male patients with DMD were included in the study. The vital capacity (VC) and maximum insufflation capacity (MIC) were measured. The unassisted peak cough flow (UPCF) and three different techniques of assisted peak cough flow were evaluated. UPCF measurements were possible for all 71 subjects. But when performing the three different assisted cough techniques, peak cough flows (PCFs) could be obtained from only 51 subjects. The mean value of MICs (1801 ± 780 cc) was higher than that of VCs (1502 ± 765 cc) (p < 0.01). All three assisted cough methods showed a significantly higher value than the unassisted method (F=80.92, p < 0.01). The manual assisted PCF under MIC (MPCFmic) significantly exceeded those produced by manual assisted PCF (MPCF) or PCF under MIC (PCFmic). The positive correlation between the MIC, VC difference (MIC-VC), and the difference between PCFmic and UPCF (PCFmic-UPCF) was seen (r=0.572, p < 0.01). The preservation of pulmonary compliance is important for the development of an effective cough as well as assisting the compression and expulsive phases. Thus, the clinical importance of the inspiratory phase and pulmonary compliance in assisting a cough should be emphasized.

Three cases of manifesting female carriers in patients with Duchenne muscular dystrophy.

Duchenne muscular dystrophy usually affects males. However, females are also affected in rare instances. Approximately 8% of female Duchenne muscular dystrophy (DMD) carriers are manifesting carriers and have muscle weakness to some extent. We investigated the clinical features of 3 female patients with dystrophinopathy diagnosed by clinical, pathological, and genetic studies at our neuromuscular disease clinic. The onset age of manifesting symptoms varied (8-28 years). Muscle weakness grade varied as follows: patient 1 showed asymmetrical bilateral proximal upper and lower extremities weakness, patient 2 showed asymmetrical bilateral upper extremities weakness similar to scapulohumoral muscular dystrophy, and patient 3 had only bilateral asymmetric proximal lower extremities weakness. Two patients had familial histories of DMD (their sons were diagnosed with DMD), but the 1 remaining patient had no familial history of DMD. The serum creatine kinase level was elevated in all patients, but it was not correlated with muscular weakness. An electromyography study showed findings of myopathy in all patients. One patient was diagnosed with a DMD carrier by a muscle biopsy with an immunohistochemical stain (dystrophin). The remaining 2 patients with familial history of DMD were diagnosed by multiplex ligation-dependent probe amplification (MLPA). There were inconsistent clinical features in the female carriers. An immunohistochemical analysis of dystrophin could be useful for female carrier patients. Also, multiplex ligation-dependent probe amplification is essential for the diagnosis of a manifesting female carrier DMD in female myopathic patients because conventional multiplex PCR could not detect the duplication and is less accurate compared to MLPA.

Comparison of Pulmonary Functions at Onset of Ventilatory Insufficiency in Patients With Amyotrophic Lateral Sclerosis, Duchenne Muscular Dystrophy, and Myotonic Muscular Dystrophy.

Objective To evaluate pulmonary functions of patients with amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD), and myotonic muscular dystrophy (MMD) at the onset of ventilatory insufficiency. Methods This retrospective study included ALS, DMD, and MMD patients with regular outpatient clinic follow-up in the Department of Rehabilitation Medicine at Gangnam Severance Hospital before the application of non-invasive positive pressure ventilation (NIPPV). The patients were enrolled from August 2001 to March 2014. If patients experienced ventilatory insufficiency, they were treated with NIPPV, and their pulmonary functions were subsequently measured. Results Ninety-four DMD patients, 41 ALS patients, and 21 MMD patients were included in the study. The mean SpO2 was lower in the MMD group than in the other two groups. The mean forced vital capacity (FVC) in the supine position was approximately low to mid 20% on average in DMD and ALS patients, whereas it was 10% higher in MMD patients. ALS patients showed a significantly lower FVC in the supine position than in the sitting position. Maximal insufflation capacity, unassisted peak cough flow, maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP) were significantly higher in MMD group than in the other groups. MEP was significantly the lowest in DMD patients, followed by in ALS, and MMD patients, in order. Conclusion Disease-specific values of pulmonary function, including FVC, MEP, and MIP, can be accurately used to assess the onset of ventilatory insufficiency in patients with ALS, DMD, and MMD.

External Control of Exhalation for Cough Assistance: A Method for Patients With Glottis Dysfunction and/or Tracheostomy

OBJECTIVE To investigate the effectiveness of our method of assisting a cough by mimicking the functions of the glottis in patients with bulbar muscle weakness or paralysis and/or those who had a tracheostomy tube. DESIGN Before-after trial. SETTING University rehabilitation hospital. PARTICIPANTS Patients (N=35) with bulbar muscle weakness or paralysis and/or those who had a tracheostomy tube. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES The unassisted peak cough flow (PCF), the assisted PCF, and the assisted PCF with the external control method mimicking glottis function by an end-inspiratory external closure of the airways. RESULTS Of the 35 patients, 13 were tracheostomized cervical cord injury patients, 11 were neuromuscular disease (NMD) patients with glottis dysfunction only, and 11 were NMD patients with a tracheostomy and glottis dysfunction. Assisted PCF with the external control method were higher than unassisted PCF and/or assisted PCF in all patients. Assisted PCF with the external control methods were measured in all of the patients even when the unassisted PCFs and/or assisted PCFs could not be measured. For patients with measurable assisted PCFs, the assisted PCF with the external control methods were significantly higher than the assisted PCFs. CONCLUSIONS We showed the effectiveness of our method of assisting a cough by external control of the glottis in patients with bulbar muscle weakness or paralysis and/or those who had a tracheostomy tube who cannot effectively cough with the help of existing cough assistance methods.

Elucidation of Relevant Neuroinflammation Mechanisms Using Gene Expression Profiling in Patients with Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by damage of motor neurons. Recent reports indicate that inflammatory responses occurring within the central nervous system contribute to the pathogenesis of ALS. We aimed to investigate disease-specific gene expression associated with neuroinflammation by conducting transcriptome analysis on fibroblasts from three patients with sporadic ALS and three normal controls. Several pathways were found to be upregulated in patients with ALS, among which the toll-like receptor (TLR) and NOD-like receptor (NLR) signaling pathways are related to the immune response. Genes—toll-interacting protein (TOLLIP), mitogen-activated protein kinase 9 (MAPK9), interleukin-1β (IL-1β), interleukin-8 (IL-8), and chemokine (C-X-C motif) ligand 1 (CXCL1)—related to these two pathways were validated using western blotting. This study validated the genes that are associated with TLR and NLR signaling pathways from different types of patient-derived cells. Not only fibroblasts but also induced pluripotent stem cells (iPSCs) and neural rosettes from the same origins showed similar expression patterns. Furthermore, expression of TOLLIP, a regulator of TLR signaling pathway, decreased with cellular aging as judged by changes in its expression through multiple passages. TOLLIP expression was downregulated in ALS cells under conditions of inflammation induced by lipopolysaccharide. Our data suggest that the TLR and NLR signaling pathways are involved in pathological innate immunity and neuroinflammation associated with ALS and that TOLLIP, MAPK9, IL-1β, IL-8, and CXCL1 play a role in ALS-specific immune responses. Moreover, changes of TOLLIP expression might be associated with progression of ALS.

Successful Surgery for Scoliosis Supported by Pulmonary Rehabilitation in a Duchenne Muscular Dystrophy Patient With Forced Vital Capacity Below 10

Low vital capacity is a risk factor for scoliosis correction operation in Duchenne muscular dystrophy (DMD) patients, but pulmonary rehabilitation, including noninvasive intermittent positive pressure ventilator application, air stacking exercise, and assisted coughing technique, reduces the pulmonary complications and perioperative mortality risk. In this case, the patients preoperative forced vital capacity (FVC) was 8.6% of normal predicted value in sitting position and 9.4% in supine position. He started pulmonary rehabilitation before the operation and continued right after the operation. Scoliosis correction operation was successful without any pulmonary complications, and his discomfort in sitting position was improved. If pulmonary rehabilitative support is provided properly, FVC below 10% of normal predicted value is not a contraindication of scoliosis correction operation in DMD patients.

Correlation of Serum Creatine Kinase Level With Pulmonary Function in Duchenne Muscular Dystrophy

Objective To investigate the relationship between serum creatine kinase (CK) level and pulmonary function in Duchenne muscular dystrophy (DMD). Methods A total of 202 patients with DMD admitted to the Department of Rehabilitation Medicine, Gangnam Severance Hospital were enrolled from January 1, 1999 to March 31, 2015. Seventeen patients were excluded. Data collected from the 185 patients included age, height, weight, body mass index, pulmonary function tests including forced vital capacity (FVC), peak cough flow, maximal expiratory pressure (MEP), and maximal inspiratory pressure (MIP), and laboratory measurements (serum level of CK, CK-MB, troponin-T, and B-type natriuretic peptide). FVC, MEP, and MIP were expressed as percentages of predicted normal values. Results Serum CK activities were elevated above normal levels, even in the oldest DMD group. Serum CK level was strongly correlated with pulmonary functions of sitting FVC (p<0.001), supine FVC (p<0.001), MIP (p=0.004), and MEP (p<0.001). Conclusion Serum CK level is a reliable screening test even in patients with advanced DMD, and is a strong predictor of pulmonary functions.

Exercise effect of modified contralateral stabilization bar during one-legged isokinetic exercise

We compared the electrical activities recorded from the muscles of the unexercised leg with changing the position of the contralateral stabilization bar to determine whether the degree of muscle contraction was influenced by the position of the bar during one-legged isokinetic exercise using an isokinetic dynamometer. The root mean square (RMS) values recorded from the medial hamstring sites of the unexercised legs showed a significantly higher value when the bar was located behind and on both in front of and behind the unexercised leg during one-legged extension exercise. Results from the isokinetic knee flexion exercise test indicated that a significantly greater RMS value was recorded from the vastus lateralis sites when the bar was located in front of and on both sides of the unexercised leg. During one-legged isokinetic extension-flexion exercise, the mean values of RMS voltage were greater when the bar was positioned in front of and on both sides of the unexercised leg in the vastus lateralis site. At the medial hamstring site, a greater value was noticed when the bar was located behind or on both sides.

Artificial external glottic device for passive lung insufflation.

Purpose For patients with neuromuscular disease, air stacking, which inflates the lungs to deep volumes, is important for many reasons. However, neuromuscular patients with severe glottic dysfunction or indwelling tracheostomy tubes cannot air stack effectively. For these patients, we developed a device that permits deep lung insufflations substituting for glottic function. Materials and Methods Thirty-seven patients with bulbar-innervated muscle weakness and/or tracheostomies were recruited. Twenty-three had amyotrophic lateral sclerosis, and 14 were tetraplegic patients due to cervical spinal cord injury. An artificial external glottic device (AEGD) was used to permit passive deep lung insufflation. In order to confirm the utility of AEGD, vital capacity, maximum insufflation capacity (MIC), and lung insufflation capacity (LIC) with AEGD (LICA) were measured. Results For 30 patients, MICs were initially zero. However, with the use of the AEGD, LICA was measurable for all patients. The mean LICA was 1,622.7±526.8 mL. Although MIC was measurable for the remaining 7 patients without utilizing the AEGD, it was significantly less than LICA, which was 1,084.3±259.9 mL and 1,862.9±248 mL, respectively (p<0.05). Conclusion The AEGD permits lung insufflation by providing deeper lung volumes than possible by air stacking.

Home Mechanical Ventilation in South Korea

Purpose To survey the use of invasive and noninvasive home mechanical ventilation (HMV) methods in South Korea from the perspective of physical medicine and rehabilitation (PM&R). Materials and Methods For 413 users of HMV, retrospective reviews of PM&R interventions and survey of HMV methods employed from Mar 2000 to Dec 2009. Results Of the 413 users, the majority of whom with progressive neuromuscular disorders (NMDs) (n=358), 284 patients initially used noninvasive mechanical ventilation (NIV), while 63 others who were using tracheostomy mechanical ventilation switched to NIV as part of their rehabilitation. The NMD patients began HMV at an earlier age (34.9±20.3 yrs), and used for longer (14.7±7.5) hours than patients with non-neuromuscular causes of respiratory impairment. Conclusion Noninvasive management was preferred over invasive ones, and transition to the former was a result of PM&R interventions.