ADSSL1 myopathy is the most common nemaline myopathy in Japan with variable clinical features

ObjectiveTo elucidate the prevalence of Japanese ADSSL1 myopathy and determine the clinicopathologic features of the disease.MethodsWe searched for ADSSL1 variants in myopathic patients from January 1978 to March 2019 in our repository and assessed the clinicopathologic features of patients with variants.ResultsWe identified 63 patients from 59 families with biallelic variants of ADSSL1. Among the 7 distinct variants identified, c.781G>A and c.919delA accounted for 53.2% and 40.5% of alleles, respectively, suggesting the presence of common founders, while the other 5 were novel. Most of the identified patients displayed more variable muscle symptoms, including symptoms in the proximal and/or distal leg muscles, tongue, masseter, diaphragm, and paraspinal muscles, in adolescence than previously reported patients. Dysphagia with masticatory dysfunction developed in 26 out of 63 patients; hypertrophic cardiomyopathy developed in 12 out of 48 patients; and restrictive ventilatory insufficiency developed in 26 out of 34 patients in later stages. Radiologically, fat infiltration into the periphery of vastus lateralis, gastrocnemius, and soleus muscles was observed in all patients. Pathologically, nemaline bodies in addition to increased lipid droplets and myofibrillar disorganization were commonly observed in all patients, suggesting that the disease may be classified as nemaline myopathy. This finding revealed that ADSSL1 myopathy is the most frequent among all genetically diagnosable nemaline myopathies in our center.ConclusionsADSSL1 myopathy is characterized by more variable manifestations than previously reported. It is the most common among all genetically diagnosable nemaline myopathies in our center, although mildly increased lipid droplets are also constantly observed features.

DCTN1-related Parkinson-plus disorder (Perry syndrome)

Dynactin-1 (DCTN1)-related Parkinson-plus disorder (Perry syndrome) is an autosomal dominant neurodegenerative disorder characterised by levodopa-resistant parkinsonism, weight loss, mood change and central hypoventilation. Ventilatory insufficiency is the predominant cause of death. It has been previously described in 87 people from 20 families with a worldwide distribution. It is now recognised as a distinct TDP-43 proteinopathy caused by a pathological mutation in DCTN1. Its rarity and clinical overlap with other neurodegenerative diseases increase the risk of delayed or incorrect diagnosis. Ventilatory support can improve life expectancy but this depends upon its recognition; overall its prognosis remains poor. We report a patient with DCTN1-related Parkinson-plus disorder, in whom genetic confirmation came only after death.

Selective screening of late-onset Pompe disease (LOPD) in patients with non-diagnostic muscle biopsies

AimsAs of 2016, there were five patients with Pompe in Slovenia (two infantile, one childhood and two adult onset) with a prevalence of 1:400 000; however, the prevalence of late-onset Pompe disease (LOPD) in some other countries means this ratio could be an underestimate. Since an LOPD muscle biopsy could be unspecific or even normal, the purpose of this study is to assess the prevalence of LOPD in patients with non-diagnostic muscle biopsies.MethodsSix hundred biopsies were recorded at the Neuromuscular Tissue Bank of the University of Ljubljana for the period 2004–2014. All adult patients with non-diagnostic muscle biopsies were invited to the National Slovenian Neuromuscular Centre for dried blood spot testing for LOPD.ResultsA total of 90 patients (56% of those invited) responded. No patient with LOPD was found. A total of 49 patients (54%) had fixed muscle weakness, 31 (34%) had mild symptoms and no weakness and 10 (11%) had asymptomatic hyperCKemia. Ventilatory insufficiency associated with proximal muscle weakness was found in two patients (2%). No patients exhibited vacuolar myopathy, globular accumulations of glycogen or regions of increased acid phosphatase activity within the sarcoplasm.ConclusionsThe study results do not support the hypothesis that LOPD is underestimated in Slovenian patients with non-diagnostic muscle biopsies; this could be consistent with the fact that LOPD is of low prevalence in Slovenia, as is the case in the populations of Finland, French-speaking Belgium, west Sweden and west Denmark.

Efficacy of new intermittent abdominal pressure ventilator for post-ischemic cervical myelopathy ventilatory insufficiency

Non-invasive ventilation (NIV) is the treatment of choice for patients symptomatic for respiratory muscle dysfunction. It can normalize gas exchange and provide up to continuous non-invasive ventilator support (CNVS) as an alternative to intubation and tracheotomy. It is usually provided via non-invasive facial interfaces or mouthpieces, but these can be uncomfortable and uncosmetic. The intermittent abdominal pressure ventilator (IAPV) has been used for diurnal ventilatory support since 1938 but has been off the market since about 1990. Now, however, with greater emphasis on non-invasive management, a new IAPV is available. A patient with chronic ventilatory insufficiency post-ischemic cervical myelopathy, dependent on sleep NVS since 2003, developed symptomatic daytime hypercapnia for which he also used diurnal NVS via nasal pillows. However, he preferred not having to use facial interfaces. When not using diurnal NVS he was becoming dyspnoeic. Diurnal use of an IAPV was introduced. Arterial blood gas analysis using the IAPV decreased his blood pH from 7.45 to 7.42, PaCO2 from 58 to 37mmHg, and improved PaO2 from 62 to 92mmHg. At discharge, the patient used the IAPV 8 h/day with improved mood and quality of life. Consequently, he returned to work as a painter.

New Developments in Mechanical Ventilation

Positive pressure ventilation was developed in the 1950s as a way to treat respiratory failure due to ventilatory insufficiency. While lifesaving, mechanical ventilation, especially when prolonged, can be associated with a host of complications. Current advances focus on strategies to liberate patients from the ventilator. New guidelines have been published to aid practitioners in this area.