Advanced Duchenne Muscular Dystrophy Research Articles

Aggravation of Cardiovascular and Respiratory Decline in Advanced Duchenne Muscular Dystrophy Complicated by Dilated Cardiomyopathy – Case Study and Review of Literature

Introduction: Duchenne muscular dystrophy is a genetic X-linked recessive disorder. This condition is characterized by progressive loss of muscle tissue. Thus, it results in deterioration and inability to perform basic motor skills such as independent movement or breathing. Due to progressive muscle weakness, patients with advanced stages of DMD require mechanical ventilation, feeding, and rehabilitation. Furthermore, alterations in cardiac muscle lead to cardiomyopathy. Despite advanced supportive treatment, DMD is a fatal disease. Purpose: The aim of the paper is to present, using a case study description, the current standards of treatment for patients with Duchenne muscular dystrophy as well as the current state of knowledge and new discoveries regarding this medical condition. Material and methods The patient's medical records were analyzed and available literature in PubMed was reviewed to write this article using the keywords: „Duchenne muscular dystrophy”; „cardiomyopathy”; „mechanical ventilation”; „gene therapy”; Conclusions Early detection of respiratory and circulatory insufficiency improves the patient's quality of life. Many patients with an advanced stage of Duchenne muscular dystrophy need specialized treatment, for example, in the intensive care unit. Therefore there is an urgent need for new treatment methods, such as gene therapies, which can slow down or break the course of the disease. New discoveries and the implementation of new treatment standards can enhance the quality of life for patients and extend their lifespans.

“I don't know whether I will be alive or not” - An interpretative phenomenological analysis of young adult males with Duchenne Muscular Dystrophy making sense of self and life

BackgroundWith ventilatory support, boys with Duchenne Muscular Dystrophy (DMD) now live longer. The emerging adulthood offers unanticipated opportunities for identity exploration. Existing literature has raised issues around transitions and implicit obligations within structural and sociological domains; intrinsic challenges are posed, while concurrently engendering possibilities in an uncertain future. ObjectiveReveal lived experience and meaning making among men with advanced DMD living outside the western context. MethodsSecondary data, essentially transcripts of semi-structured interviews with five young men with DMD, age ranging from 23 to 37 years, conducted as part of a larger study were analysed iteratively in depth. Given their underlying vulnerability associated with significant physical dependencies, all respondents were receiving palliative care from the local hospice, and lived with family caregivers at home. ResultsThree themes encapsulated the essence of their lifeworld at this juncture. Each shared poignant stories of having survived adverse circumstances in the past, learning to live with themselves in the current state of disabilities and disconnection with peers. Yet, moments of yearning surface, to make new friends and find gainful employment like everyone else. Ambivalence notwithstanding, they navigated societal marginalization through digital media, or found meaning in family bonding and existential dimensions. Faced with uncertainty, most embraced the status quo in silent resignation, to minimise disappointment or as pragmatic responses to enduring systemic and personal barriers. ConclusionsStudy findings expounded challenges men with advanced DMD grappled that ultimately shaped self-identity. Healthcare professionals could support this group of precarious survivors even better through individualised person-centred care.

Polysymptomatology and Polypharmacy at End of Life in Patients with Duchenne Muscular Dystrophy

To characterize symptom frequency and symptom-directed treatment approaches in patients who died with advanced Duchenne muscular dystrophy (DMD). This was a retrospective cohort study of patients in a multidisciplinary DMD program who died between January 1, 2013, and June 30, 2021. Inclusion criteria were patients who died with advanced DMD in the time period studied; exclusion criteria were low exposure to palliative care (<2 encounters). Demographic, symptom, and end-of-life data, as well as medications used for symptom management, were abstracted from the electronic medical record. In total, 15 patients were eligible for analysis. The median age of death was 23years (range 15-30 years). One (6.7%) experienced a full code at death, 8 (53.3%) had do-not-resuscitate orders, and 4 (26.7%) had limited do-not-resuscitate orders. Mean palliative care exposure was 1280days. All 15 (100%) had pain and dyspnea; 14 (93.3%) anorexia, constipation, and sleep difficulty; 13 (86.7%) wounds; and 12 (80%) anxiety and nausea/vomiting. Multiple medications and drug classes were used to target symptoms. We found significant polysymptomatology and polypharmacy in patients who died with advanced DMD. Clinicians who care for patients with advanced DMD should clarify goals of care and document advance care planning. Given the complexity of multisystem disease progression, palliative care should provide subspecialty pain management and assist with psychosocial burdens.

Correlation of Bone Mineral Density with Pulmonary Function in Advanced Duchenne Muscular Dystrophy.

A relationship between bone mineral density (BMD) and physical function has been revealed in the general population and various diseases. However, there is a lack of research investigating the correlation between BMD and respiratory function, one of few measurable physical parameters in patients with advanced Duchenne muscular dystrophy (DMD). To determine whether pulmonary function parameters, including respiratory muscle strength, are related to BMD. Retrospective observational study. A tertiary university hospital. DMD patients who were over 20 years of age, nonambulatory, and supported by mechanical ventilators. The patients' age, weight, and pulmonary function as well as the BMD of the first and the fourth lumbar vertebra were assessed. Pulmonary function includes forced vital capacity (FVC), unassisted and assisted peak cough flow (UPCF and APCF), maximal expiratory pressure (MEP), and maximal inspiratory pressure (MIP). A bivariate correlation for BMD and other pulmonary parameters was calculated, and hierarchical regression analysis was used to determine predictors of spine Z-score. It was observed that the decrease in the spine BMD was not significantly correlated with age. However, the body mass index (BMI) and all parameters of pulmonary function were correlated with BMD. Partial correlation analysis adjusted by BMI showed that UPCF and APCF were powerful predictors of spine BMD. The BMD of the lumbar spine correlated with BMI and PCF in patients with DMD at an advanced stage.

Relationship between Eating and Digestive Symptoms and Respiratory Function in Advanced Duchenne Muscular Dystrophy Patients.

Background:Duchenne muscular dystrophy (DMD) patients can have various issues that affect their quality of life, including eating and digestive conditions.Objective:We sought to identify the relationship between respiratory function and various eating and digestion related symptoms in patients with advanced Duchenne muscular dystrophy (DMD).Methods:Eating and digestive symptoms, including loss of appetite, nausea, vomiting, diarrhea, constipation, swallowing difficulty, mastication difficulty, early satiety, and aspiration, were evaluated among patients with advanced DMD who were nonambulatory and required noninvasive mechanical ventilatory support. In addition, various respiratory function parameters were measured, including forced vital capacity (FVC), maximal insufflation capacity (MIC), peak cough flow (PCF), assisted PCF (APCF), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP). We then analyzed the relationship between gastrointestinal symptoms and respiratory function parameters.Results:A total of 180 patients (age, 22.3±5.0 years) were included in the analysis. Loss of appetite and early satiety showed no correlation with any of the respiratory function parameters. Constipation was correlated with MEP; swallowing difficulty was correlated with MIC, APCF, MIP and MEP; and mastication difficulty was correlated with FVC, PCF, APCF, MIP, and MEP. Notably, age did not correlate with any gastrointestinal symptoms.Conclusions:Eating and digestive symptoms are more closely correlated with respiratory function than with age in patients with DMD. We think this correlation is mainly caused by the skeletal muscle strength, which is major determinant of both digestive and respiratory function.

Can radial bone mineral density predict spinal bone mineral density in patients with advanced Duchenne muscular dystrophy?

In advanced Duchenne muscular dystrophy (DMD), patients with high bone fracture risk due to osteoporosis, it is difficult to measure spinal bone mineral density (BMD) because of maintaining proper posture. This study began with the idea that if we diagnose and manage osteoporosis by predicting spinal BMD through easily testable radial BMD, we could prevent fracture and improve quality of life in DMD patients. In 61 DMD patients aged 20 years or older who were admitted to Gangnam Severance Hospital from April 2013 to May 2015, radial BMD and spinal BMD were measured to compare their Z-scores. In 45 patients, the z-score was less than −2.0 in spinal BMD defined as osteoporosis. And the optimal range of Z-score in the radius was −5.2 to −5.0 (sensitivity 78.9%, specificity 71.4%). Only through the radius BMD, spinal BMD can be predicted and we suggest appropriate times for treatments.

Renal dysfunction is rare in Fukuyama congenital muscular dystrophy

BackgroundThe leading cause of death in patients with Fukuyama congenital muscular dystrophy (FCMD) is congestive heart failure or respiratory dysfunction, which is same as that in Duchenne muscular dystrophy (DMD). Recent studies reported that renal dysfunction is a common complication and an increasing cause of death in advanced DMD. It can be attributable to circulatory instability or inappropriate use of drugs for treating cardiac dysfunction. MethodsWe retrospectively evaluated renal function in 38 genetically diagnosed patients with FCMD (range, 1.3–32.9 years; mean age, 13.7 ± 6.9 years) using cystatin C. We examined possible relationships of cystatin C with blood natriuretic peptide and creatinine levels along with cardiac echocardiography findings. ResultsTwenty-five patients were treated for cardiac dysfunction. Elevated cystatin C level was detected only in two, who also showed proteinuria, glycosuria, hematuria, and extremely high β2-microglobulin levels on urine tests, and were thus diagnosed with renal tubular cell damage. Because both patients were treated for intractable epilepsy with various antiepileptic drugs, including valproic acid (VPA), and had low serum carnitine levels, renal tubular cell damage was considered as an adverse effect of VPA. Unlike patients with DMD, no patient with FCMD had renal dysfunction. Such a rare occurrence of renal dysfunction can be attributable to mild cardiac dysfunction, short disease duration, and careful and early fluid management. ConclusionRenal dysfunction is rare in patients with FCMD; however, renal tubular cell damage should be ascertained, particularly in those undergoing VPA treatment for epilepsy.

Percutaneous endoscopic gastrostomy procedure in patients with advanced duchenne muscular dystrophy

Background: The placement of percutaneous endoscopic gastrostomy (PEG) is the first choice procedure for long-term management of progressive dysphagic patients with Duchenne muscular dystrophy (DMD), but severe respiratory failure often makes the patients to give it up. We established a safe PEG procedure for patients with neuromuscular diseases using urtra-thin gastrointestinal tract endoscope from 2005.

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

ObjectiveTo investigate the relationship between serum creatine kinase (CK) level and pulmonary function in Duchenne muscular dystrophy (DMD).MethodsA 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.ResultsSerum 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).ConclusionSerum CK level is a reliable screening test even in patients with advanced DMD, and is a strong predictor of pulmonary functions.

Utility of skinfold thickness measurement in non-ambulatory patients with Duchenne muscular dystrophy

Nutritional disorders in Duchenne muscular dystrophy (DMD) worsen the medical condition. In particular, obesity is a serious problem that increases the risk of cardiomyopathy and affects nursing care. However, it is often difficult to evaluate body fatness in the advanced stages of DMD. Skinfold thickness measurement is a classical method to evaluate body fatness and is easily performed, even for bed-bound patients at home. We aimed to investigate the utility of skinfold thickness measurement in non-ambulatory DMD patients. Twenty-two patients with non-ambulatory, steroid-naive DMD ranging in age of 12–47 years were evaluated by body mass index (BMI), blood tests, measurement of triceps skinfold thickness (TSF), and abdominal computed tomography (CT) measurement of the areas of both subcutaneous and visceral fat. TSF showed good correlation with BMI (r = 0.80; p < 0.001), serum triglycerides (r = 0.67; p < 0.01), area of subcutaneous fat (r = 0.85; p < 0.0001), and area of visceral fat (r = 0.76; p < 0.0001). These results indicate the skinfold thickness measurement may be applicable as a screening tool in clinical practice where CT and magnetic resonance imaging assessment is often difficult in patients with advanced DMD.

G.P.115: Pooled analyses of efficacy parameters in patients with Duchenne muscular dystrophy (DMD): Results from the drisapersen (DRIS) clinical trial programme

DRIS is a 2′-O-methyl-phosphorothioate antisense oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA of boys with DMD. In a Ph 3 study (DMD114044), a 10 m treatment difference (NS) on 6-min walking distance (6MWD) in favour of DRIS was seen in the overall study population but there was a treatment benefit of 21 m in a pre-specified subset of boys aged ⩽7y (n = 79), suggesting that younger, less progressed boys could benefit more from DRIS in terms of ambulatory endpoints vs older boys in whom DMD is more advanced. In an open-label extension (OLE; DMD114349) of two 48-wk placebo (PBO)-controlled trials (DMD114117, DMD114044), 96 wks’ DRIS resulted in a clinically meaningful difference from 48 wks’ PBO (feeder study) followed by DRIS (OLE) in 6MWD of 46 m (n = 113; completed 48 wks’, DMD114349). By feeder study, the treatment effect was 52 m (n = 30) for DMD114117 and 49 m for DMD114044 (n = 83), for those on DRIS for 96 wks vs PBO/delayed treatment. Data suggest that treatment benefits that manifest early in less severe DMD are maintained, while in more advanced DMD, benefits may emerge only after prolonged exposure. In a pooled analysis of two comparable Ph 2 trials (DMD114117, DMD114876), a subset of boys with similar BL demographic and functional characteristics who received DRIS 6 mg/kg/wk (n = 36) was compared with PBO-treated boys (n = 34; Mixed-Effect Model Repeated Measure model including Treatment, Visit, Treatment by Visit, Country/Study, BL 6MWD, BL 6MWD by Visit). At Wk 24, there was a clinically meaningful and statistically significant difference in 6MWD between DRIS- and PBO-treated boys of 31 m (n = 70; 95% confidence interval: 11, 51; p = 0.003), based on an adjusted mean (standard error) difference of −11(7) m for placebo and + 20(7) m for DRIS. DMD114044 enrolled boys aged ⩽16y, whereas in the pooled dataset, the oldest boys were only 13y, supporting the premise that treatment at a younger age is more immediately beneficial for preserving ambulatory capacity.

G.P.317: Renal dysfunction in patients with Fukuyama congenital muscular dystrophy

Fukuyama congenital muscular dystrophy (FCMD), characterized by intellectual deficits and epilepsy with cortical migration defects, is the most common congenital muscular dystrophy in Japan. Most patients die of congestive heart failure or respiratory dysfunction, as in Duchenne muscular dystrophy (DMD), in the second decade of life. Recent studies have found that renal dysfunction is a common complication of advanced DMD and is the third leading cause of death in these patients. Circulatory instability caused by cardiac dysfunction is thought to result in renal dysfunction, especially prerenal failure. We retrospectively evaluated renal function in 37 genetically diagnosed FCMD patients (1.3–32.9 years, mean age 13.7 ± 6.9 years) using Cystatin C. We examined possible relationships of Cystatin with the levels of blood natriuretic peptide and creatinine, as well as the cardiac echo results. Twenty-four patients were treated for cardiac dysfunction, but elevated Cystatin C was detected in only two. These two patients also showed proteinuria, glycosuria, hematuria and extremely high levels of β2-microglobulin on urine tests and were thus diagnosed as having kidney tubule cell damage. Since both patients were treated for intractable epilepsy with many types of antiepileptic drugs, including valproic acid (VPA), and had low serum carnitine levels, kidney tubule cell damage was thought to be an adverse effect of VPA. One patient improved in response to a reduced VPA dose, but the other developed Fanconi syndrome. Unlike DMD patients, none of our FCMD patients progressed to prerenal failure. Though FCMD patients also have cardiac dysfunction, careful fluid management is instituted early because dysphagia emerges in the early stage. In DMD patients, inadequate fluid management may also cause circulatory instability, which can progress to prerenal failure. On the other hand, kidney tubule cell damage should be noted in FCMD patients especially with VPA treatment for epilepsy.

Ultra-widefield Imaging of Duchenne Muscular Dystrophy–associated Proliferative Retinal Vasculopathy Improved With Panretinal Laser Photocoagulation Alone

Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder whose ophthalmic associations most commonly consist of pigmentary fundus changes and scotopic electroretinogram abnormalities. A 23-year-old man with advanced DMD and associated cardiopulmonary compromise complaining of floaters presented with a striking retinal vasculopathy characterized by vitreous hemorrhage, neovascularization, capillary drop-out, and prominent saccular venular aneurysms diffusely throughout the fundus of both eyes. This vasculopathy was promptly treated with panretinal phocoagulation with marked improvement to at least 1 year. This report suggests that early identification and prompt treatment of DMD may be important in managing this condition.

Tracheotomy bleeding from an unusual tracheo-arterial fistula: involvement of an aberrant right subclavian artery

The development of a tracheo-arterial fistula is a rare but severe complication of tracheotomy. The reported patient presented with such a fistula involving an aberrant right subclavian artery, termed an arteria lusoria, an aortic arch abnormality which is usually asymptomatic. A 30-year-old man was admitted to our institution for bleeding through his tracheotomy. He had been treated for advanced Duchenne muscular dystrophy, involving invasive assisted ventilation, since the age of 10 years. Surgical exploration and computed tomography scanning revealed a tracheo-arterial fistula involving an aberrant right subclavian artery, associated with severe scoliosis. Emergency, transient haemostasis was achieved by over-inflation of the tracheostomy tube cuff. Aneurysm ablation was successfully achieved as the result of an endovascular interventional radiology procedure. Arteria lusoria is one of the most common aortic arch abnormalities. The occurrence of an aneurysm of this artery in a tracheotomised patient has not previously been described. In Duchenne muscular dystrophy patients, spinal deformities may result in thoracic compression, which may alter the anatomical relations of mediastinal vessels. Such deformities are slowly progressive. Thus, vigilance is required in the long term management of Duchenne muscular dystrophy patients with a tracheostomy.

Respiratory disorders during sleep in Duchenne muscular dystrophy

Respiratory disorders during sleep were studied in 42 patients with Duchenne muscular dystrophy (DMD) (mean age 18.4 years). Chest and abdominal movement, nasal airflow, snoring sounds, eye movement, and oxygen saturation were monitored during sleep. Three patterns of disorders were found: obstructive apnea, central apnea, and paradoxical respiration without upper airway obstruction (non-obstructive paradoxical respiration). Of these three patterns, obstructive apnea was the most common. Hypertrophy of the tongue and collapsibility of the upper airway seemed to be responsible for the obstructive apnea in these patients. The relationships between PaCO2 while breathing room air and the various indices of respiratory disorders were studied. The index of central apnea differed significantly between patients in whom PaCO2 was less than 50 Torr (early disease, n = 22) and those in whom PaCO2 was greater than or equal to 50 Torr (advanced disease, n = 20), but the indices of obstructive apnea and non-obstructive paradoxical respiration did not differ between those two groups. In conclusion, sleep disorders were common in patients with DMD, and the most common was obstructive apnea. In the patients with advanced DMD, blood gas analysis showed hypercapnia, and the index of central sleep apnea was high, probably because of respiratory muscle weakness or abnormalities in the respiratory center.

Influence of Disease Progression on the Neuromuscular Blocking Effect of Mivacurium in Children and Adolescents with Duchenne Muscular Dystrophy

Studies with nondepolarizing neuromuscular blocking agents showed a delayed onset and prolonged recovery in patients with Duchenne muscular dystrophy. The objective of this study was to investigate if these alterations depend on disease progression. The authors studied 11 children (6-9 yr) with moderate Duchenne muscular dystrophy, 11 adolescents (12-16 yr) with advanced Duchenne muscular dystrophy, and 2 age-matched control groups of 8 patients each (5-9 and 10-17 yr). Anesthesia was performed with propofol and remifentanil. Patients received a single intravenous dose of 0.2 mg/kg mivacurium. Neuromuscular transmission was monitored by acceleromyography. The time course of neuromuscular blockade was characterized by the onset time and the times to different levels of recovery. Onset and duration of neuromuscular blockade were significantly prolonged in adolescent Duchenne muscular dystrophy patients (onset time, 4.0 min; recovery index, 12.3 min; median), as compared with Duchenne muscular dystrophy children (onset time, 2.3 min; recovery index, 6.8 min), and also as compared with young controls (onset time, 2.0 min; recovery index, 4.4 min) and adolescent controls (onset time, 2.5 min; recovery index, 4.8 min). Within the Duchenne muscular dystrophy patients, onset time and recovery index increased significantly with age. In the control group, age had no effect. The neuromuscular blocking effects of mivacurium showed a significant age dependency in Duchenne muscular dystrophy patients, which was most probably caused by the progression of the disease.

Diagnostic utility of skin biopsy in dystrophinopathies

Aims Muscle biopsy is an important diagnostic modality and screening test for the diagnosis of dystrophinopathies. Sometimes muscle biopsies are needed for the diagnosis when genetic tests are inconclusive and are also useful for immunoblotting assay of the dystrophin protein. However, the procedure is painful, requires anesthesia and sometimes needs to be repeated. This study was undertaken to elucidate the role of skin biopsy in the diagnosis of dystrophinopathies and to validate if it can be utilized as a useful adjunct/replacement for the muscle biopsy. Methods Paired skin and muscle biopsies were studied from 39 patients with Duchenne muscular dystrophy (DMD), 4 patients with Becker's muscular dystrophy (BMD) and 37 controls. Immunostaining for dystrophin and utrophin was done on frozen sections of the test group and controls and their staining pattern in skin biopsies was compared with corresponding muscle biopsies. Results Immunostaining for dystrophin was negative in the skin biopsies of all patients (39/39, 100%) with DMD and was only weakly expressed in skin of BMD patients (4/4, 100%). Dystrophin was strongly expressed on arrector pili muscle cells of all control patients (94.6%) except two cases in whom it was weakly expressed. Utrophin was expressed on the arrector pili muscle cells of DMD patients (39/39, 100%) as well as controls (30/37, 81.1%). Conclusion Our study suggests that skin biopsy is very useful for the diagnosis of dystrophinopathies and their differentiation from other muscle diseases. It has high degrees of sensitivity, specificity, and positive and negative predictive values. It can be a useful adjunct/replacement for the muscle biopsy especially when repeated biopsies are required for monitoring therapy or in patients with advanced DMD where extreme fibrosis, adipose tissue infiltration and inflammation make interpretation of the muscle biopsy difficult. Skin biopsy is a simple, cost effective, less invasive and less traumatic diagnostic procedure when compared with muscle biopsy. This is even more pertinent because patients with muscular dystrophies have a higher risk for any form of general anesthesia. A smaller scar and fewer chances of infection at the site of biopsy are other additional advantages of skin biopsy over muscle biopsy.

G.P.12.05 Gastrostomy tube feeding in patients with severe Duchenne muscular dystrophy

To evaluate effects, risks and the indication of percutaneous endoscopic gastrostomy (PEG) for severe Duchenne muscular dystrophy (DMD), we reviewed clinical records of 21 patients with advanced DMD with gastrostomy in National Hospital Organization Nishitaga Hospital, Sendai, Japan. Mean age and mean body weight of the patients at the time of procedure were 29.3 years old and 26.2kg, respectively. All patients were advanced and severe cases of DMD who had feeding problems such as swallowing difficulties, prolonged meal time, and weight loss.

Der Punctum Plug als therapeutische Option des retrograden Aeroflows des Saccus lacrimalis

The causes of keratoconjunctivitis sicca are multifarious. Major causes include eyelid anomalies, Sjögren's disease, injuries, radiation or mucin deficiency. In our case, nasal positive airway pressure due to muscular dystrophy is described as another possible cause. A 32-year-old male patient with advanced Duchenne muscular dystrophy requires nasal continuous positive airway pressure ventilation due to loss of the auxiliary respiratory muscles. The patient presented because permanent air flow from the lower right lacrimal point resulted in epiphora and keratoconjunctivitis sicca on the right side. We reversibly occluded the lower lacrimal duct with a punctum plug flow regulator. The lacrimal flow regulator is available in two sizes, 0.8 and 0.9 mm, and is designed to be inserted into the punctal aperture. The soft silicone plug is delivered with a disposable dilator and can be used on an outpatient basis. It is actually used for punctal occlusion in patients with chronic dry eye syndrome and regulates the flow of lacrimal fluid. After insertion of a 0.9 mm punctal plug, the patient reported marked improvement of the findings, which was confirmed in a follow-up after 4 and 8 weeks. On a visual analog scale of 1 to 10, the subjective status was given a rating of 8. By occluding the right lower lacrimal point with a punctal plug, we were able to markedly reduce the unpleasant retrograde air flow and the subjective complaints of the patient with nasal continuous positive airway pressure ventilation.

Diaphragmatic function in advanced Duchenne muscular dystrophy

The aim of this study was to assess diaphragm electrical activation and diaphragm strength in patients with advanced Duchenne muscular dystrophy during resting conditions. Eight patients with advanced Duchenne muscular dystrophy (age of 25±2 years) were studied during tidal breathing, maximal inspiratory capacity, maximal sniff inhalations, and magnetic stimulation of the phrenic nerves. Six patients were prescribed home mechanical ventilation (five non-invasive and one tracheotomy). Transdiaphragmatic pressure and diaphragm electrical activation were measured using an esophageal catheter. During tidal breathing (tidal volume 198±83 ml, breathing frequency 25±7), inspiratory diaphragm electrical activation was clearly detectable in seven out of eight patients and was 12±7 times above the noise level, and represented 45±19% of the maximum diaphragm electrical activation. Mean inspiratory transdiaphragmatic pressure during tidal breathing was 1.5±1.2 cmH 2O, and during maximal sniff was 7.6±3.6 cmH 2O. Twitch transdiaphragmatic pressure deflections could not be detected. This study shows that despite near complete loss of diaphragm strength in advanced Duchenne muscular dystrophy, diaphragm electrical activation measured with an esophageal electrode array remains clearly detectable in all but one patient.