Myasthenia gravis (MG) and congenital myasthenic syndromes (CMS) are a group of disorders with a well characterised autoimmune or genetic and neurophysiological basis. We reviewed the literature from ...the last 20 years assessing the utility of various neurophysiological, immunological, provocative and genetic tests in MG and CMS. Diagnostic sensitivity of repetitive nerve stimulation test ranges between 14 and 94% and specificity between 73 and 100%; sensitivity of single-fibre EMG (SFEMG) test ranges between 64 and 100% and specificity between 22 and 100%; anti-acetylcholine receptor (AChR) antibody sensitivity ranges from 13 to 97% and specificity ranges from 95 to 100%. Overall, SFEMG has the highest sensitivity while positive anti-AChR antibodies have the highest specificity. Newer testing strategies that have been investigated over the last couple of decades include ocular vestibular-evoked myogenic potentials, otoacoustic emissions and disease-specific circulating miRNAs in serum for autoimmune myasthenia, as well as next-generation sequencing for genetic testing of CMS. While there has been significant progress in developing newer testing strategies for diagnosing MG and CMS over the last couple of decades, more research is needed to assess the utility of these newer tools regarding their sensitivity and specificity.
Amyotrophic lateral sclerosis, also known as motor neuron disease, is a fatal neurodegenerative disease. Neuromuscular respiratory failure is the commonest cause of death, usually within two to five ...years of the disease onset. Supporting respiratory function with mechanical ventilation may improve survival and quality of life. This is the first update of a review first published in 2009.
The primary objective of the review is to examine the efficacy of mechanical ventilation (tracheostomy and non-invasive ventilation) in improving survival in ALS. The secondary objectives are to examine the effect of mechanical ventilation on functional measures of disease progression and quality of life in people with ALS; and assess adverse events related to the intervention.
We searched The Cochrane Neuromuscular Disease Group Specialized Register (1 May 2012), CENTRAL (2012, Issue 4), MEDLINE (January 1966 to April 2012), EMBASE (January 1980 to April 2012), CINAHL Plus (January 1937 to April 2012), and AMED (January 1985 to April 2012). We also searched for ongoing studies on ClinicalTrials.gov.
Randomised and quasi-randomised controlled trials involving non-invasive or tracheostomy assisted ventilation in participants with a clinical diagnosis of amyotrophic lateral sclerosis, independent of the reported outcomes. We planned to include comparisons with no intervention or the best standard care.
For the original review, four authors independently selected studies for assessment and two authors reviewed searches for this update. All authors extracted data independently from the full text of selected studies and assessed the risk of bias in studies that met the inclusion criteria. We attempted to obtain missing data where possible. We planned to collect adverse event data from included studies.
For the original Cochrane review, the review authors identified and included two randomised controlled trials involving 54 participants with ALS receiving non-invasive ventilation. There were no new randomised or quasi-randomised controlled trials at this first update.Incomplete data were published for one study and we contacted the trial authors who were not able to provide the missing data. Therefore, the results of the review were based on a single study of 41 participants that compared non-invasive ventilation with standard care. It was a well conducted study with low risk of bias.The study showed that the overall median survival was significantly different between the group treated with non-invasive ventilation and the standard care group. The median survival in the non-invasive ventilation group was 48 days longer (219 days compared to 171 days for the standard care group (estimated 95% CI 12 to 91 days, P = 0.0062)). This survival benefit was accompanied by an enhanced quality of life. On subgroup analysis, the survival and quality of life benefit was much more in the subgroup with normal to moderately impaired bulbar function (20 participants); median survival was 205 days longer (216 days in NIV group versus 11 days in the standard care group, P = 0.0059). Non-invasive ventilation did not prolong survival in participants with poor bulbar function (21 participants), although it showed significant improvement in the mean symptoms domain of the Sleep Apnoea Quality of Life Index but not in the Short Form-36 Health Survey Mental Component Summary score. Neither trial reported clinical data on intervention related adverse effects.
Evidence from a single randomised trial of non-invasive ventilation in 41 participants suggests that it significantly prolongs survival and improves or maintains quality of life in people with ALS. Survival and some measures of quality of life were significantly improved in the subgroup of people with better bulbar function, but not in those with severe bulbar impairment. Future studies should examine the health economics of NIV and factors influencing access to NIV. We need to understand the factors, personal and socioeconomic, that determine access to NIV.
Amyotrophic lateral sclerosis, also known as motor neuron disease, is a fatal neurodegenerative disease. Without mechanical ventilation, death from respiratory failure usually follows within two to ...five years of the onset of symptoms.
To examine the efficacy of mechanical ventilation (tracheostomy and non-invasive ventilation) in improving survival, on disease progression and quality of life in amyotrophic lateral sclerosis.
We searched The Cochrane Neuromuscular Disease Group Trials Specialized Register (December 8 2008), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2008), MEDLINE (January 1966 to December 2008), EMBASE (January 1947 to December 2008), CINAHL Plus (January 1937 to December 2008), and AMED (January 1985 to December 2008). We also searched for ongoing studies on clinicaltrials.gov.
Randomised and quasi-randomised controlled trials involving non-invasive or tracheostomy assisted ventilation in participants with a clinical diagnosis of amyotrophic lateral sclerosis.
Four authors independently selected studies for assessment. All authors extracted data independently from the full text of selected studies and assessed the risk of bias in studies that met the inclusion criteria. We attempted to obtain missing data where possible.
Two randomised controlled trials involving 54 participants receiving non-invasive ventilation were identified and included. Incomplete data were published for one study and we contacted the trial authors who were not able to provide the missing data. Therefore the results of the review were based on a single study of 41 participants. The study showed that the overall median survival in the whole cohort after initiation of assisted ventilation was significantly different between the non-invasive ventilation and standard care groups (P = 0.0062) with a median survival for the non-invasive ventilation group patients of 48 days longer than the standard care group participants. Non-invasive ventilation significantly improved survival and quality of life in the subgroup with normal to moderately impaired bulbar function. Non-invasive ventilation did not prolong survival in patients with poor bulbar function although it showed significant improvement in the mean symptoms domain of the sleep apnoea quality-of-life index but not in the Short Form-36 quality of life mental component summary score .
Evidence from a single randomised trial of non-invasive ventilation in 41 participants suggests that it significantly prolongs survival and improves or maintains quality of life in people with ALS. Survival and some measures of quality of life were significantly improved in the subgroup of people with better bulbar function, but not in those with severe bulbar impairment.
Previous studies have described the clinical, serological and pathological features of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and antibodies directed against ...the paranodal proteins neurofascin-155, contactin-1 (CNTN1), contactin-associated protein-1 (Caspr1), or nodal forms of neurofascin. Such antibodies are useful for diagnosis and potentially treatment selection. However, antibodies targeting Caspr1 only or the Caspr1/CNTN1 complex have been reported in few patients with CIDP. Moreover, it is unclear if these patients belong to the same pathophysiological subgroup. Using cell-based assays in routine clinical testing, we identified sera from patients with CIDP showing strong membrane reactivity when both CNTN1 and Caspr1 were co-transfected (but not when CNTN1 was transfected alone). Fifteen patients (10 male; aged between 40 and 75) with antibodies targeting Caspr1/CNTN1 co-transfected cells were enrolled for characterization. The prevalence of anti-Caspr1/CNTN1 antibodies was 1.9% (1/52) in the Sant Pau CIDP cohort, and 4.3% (1/23) in a German cohort of acute-onset CIDP. All patients fulfilled European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite diagnostic criteria for CIDP. Seven (47%) were initially diagnosed with Guillain-Barré syndrome due to an acute-subacute onset. Six (40%) patients had cranial nerve involvement, eight (53%) reported neuropathic pain and 12 (80%) ataxia. Axonal involvement and acute denervation were frequent in electrophysiological studies. Complete response to intravenous immunoglobulin was not observed, while most (90%) responded well to rituximab. Enzyme-linked immunosorbent assay (ELISA) and teased nerve fibre immunohistochemistry confirmed reactivity against the paranodal Caspr1/CNTN1 complex. Weaker reactivity against Caspr1 transfected alone was also detected in 10/15 (67%). Sera from 13 of these patients were available for testing by ELISA. All 13 samples reacted against Caspr1 by ELISA and this reactivity was enhanced when CNTN1 was added to the Caspr1 ELISA. IgG subclasses were also investigated by ELISA. IgG4 was the predominant subclass in 10 patients, while IgG3 was predominant in other three patients. In conclusion, patients with antibodies to the Caspr1/CNTN1 complex display similar serological and clinical features and constitute a single subgroup within the CIDP syndrome. These antibodies likely target Caspr1 primarily and are detected with Caspr1-only ELISA, but reactivity is optimal when CNTN1 is added to Caspr1 in cell-based assays and ELISA.
Summary Although amyotrophic lateral sclerosis and its variants are readily recognised by neurologists, about 10% of patients are misdiagnosed, and delays in diagnosis are common. Prompt diagnosis, ...sensitive communication of the diagnosis, the involvement of the patient and their family, and a positive care plan are prerequisites for good clinical management. A multidisciplinary, palliative approach can prolong survival and maintain quality of life. Treatment with riluzole improves survival but has a marginal effect on the rate of functional deterioration, whereas non-invasive ventilation prolongs survival and improves or maintains quality of life. In this Review, we discuss the diagnosis, management, and how to cope with impaired function and end of life on the basis of our experience, the opinions of experts, existing guidelines, and clinical trials. We highlight the need for research on the effectiveness of gastrostomy, access to non-invasive ventilation and palliative care, communication between the care team, the patient and his or her family, and recognition of the clinical and social effects of cognitive impairment. We recommend that the plethora of evidence-based guidelines should be compiled into an internationally agreed guideline of best practice.
In adults, muscle disease (MD) is typically a chronic long-term condition that can lead to a reduced quality of life (QoL). Previous research suggests that a psychological intervention, in particular ...Acceptance and Commitment Therapy (ACT), may help improve QoL for individuals living with chronic conditions such as MD.
This nested qualitative study was incorporated within a randomized controlled trial which evaluated a guided self-help ACT intervention for people living with MD to explore their experiences of the intervention. Semi-structured interviews (
= 20) were conducted with those who had received ACT. Data were analyzed via thematic analysis.
There were four overarching themes. (1) Views on whether therapy sessions would help with a medical condition: participants' expectations regarding ACT varied. Some participants were skeptical about mindfulness. (2) I was able to look at things in a different way: participants described increased meaningful activity, greater awareness of thoughts and emotions and acceptance or adaptation to mobility problems. Some described improvement in the quality of relationships and a sense of feeling free. (3) Treating the body and the mind together: following the intervention participants noted that a holistic approach to healthcare is beneficial. (4) Intervention delivery: The remote delivery was generally seen as helpful for practical reasons and allowed participants to speak openly. Participants voiced a need for follow-up sessions.
Overall, the intervention was experienced as acceptable. Suggested improvements included de-emphasizing the role of mindfulness and adding follow-up sessions.
Background/Aim. Determining the value of Gissane?s angle (GA) plays a role in the diagnosis and prognosis of heel fractures, determining treatment methods, and assessing the outcome of surgical ...treatment. Normal values of the GA vary in relation to ethnicity, age, and gender of the examined group, which indicates its anthropometric significance. The aim of this study was to determine the range of normal GA values in the population of Central Serbia. Methods. GA was determined on lateral radiography of the foot of 145 subjects of both sexes (67 women and 78 men), with subjects divided into 6 age groups. The patients included in the study did not have a calcaneus fracture. The obtained results were processed in the Graph Pad program. Results. The average value of GA in Central Serbia was 110.8? ? 8.1?, ranging from 93? to 132.9?. The mean value of GA decreased with age, and no difference was observed between women and men, except in the youngest age group, where women had higher GA values than men. Conclusion. The results of the study showed a wide range of normal GA values, as well as the existence of a difference in subjects of different ages and sex.
Background/Aim. Coxarthrosis is a chronic degenerative joint disorder which occurs in approximately 4% of population, and bilateral occurrence is estimated at 42%. Patients with bilateral ...coxarthrosis can undergo bilateral hip replacement in one or two stage procedure. Aim of this article was to present our experience in simultaneous bilateral hip arthroplasty, and to recommend it in patients with adequate indications. Methods. We processed data for 113 patients of both genders, operated at the Clinic for Orthopedic Surgery and Traumatology of the Military Medical Academy in Belgrade, Serbia from 2005 until 2015 where single stage bilateral hip arthroplasty was performed. Identical operative technique was applied in all patients as well as standard antibiotic and thromboprophylactic treatment. Follow-up period was 30 days postoperatively. Results. Mean age of patients was 56 ? 10.2 years, whereby 45 (39.8%) of them were males and 68 (60.2%) females. Primary coxarthrosis was etiologic factor for the majority of patients, 69 (61.1%). Postoperative hospitalization duration was 10.3 days on average (range from 3 to 34 days). We noticed the following complications: one luxation of the endoprosthesis, one deep infection and one thrombosis of the leg. There was no mortality. Majority of operated patients were grouped as the American Society of Anesthesiologists (ASA) scores 1-3. Mean blood transfusion was 1,275 mL (range from 300 to 2,830 mL). Conclusion. One stage bilateral hip arthroplasty can be performed routinely and safely in facilities with possibility for interdisciplinary approach and adequate selection of patients. Data from our study which indicate significantly increased need for blood substitution, emphasize the need to introduce contemporary perioperative blood loss management principles. The rate of complications observed in our study was within rates published in the literature concerning hip arthroplasty.
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Abstract
Amyotrophic lateral sclerosis is a progressive and devastating neurodegenerative disease. Despite decades of clinical trials, effective disease-modifying drugs remain scarce. To understand ...the challenges of trial design and delivery, we performed a systematic review of Phase II, Phase II/III and Phase III amyotrophic lateral sclerosis clinical drug trials on trial registries and PubMed between 2008 and 2019. We identified 125 trials, investigating 76 drugs and recruiting more than 15 000 people with amyotrophic lateral sclerosis. About 90% of trials used traditional fixed designs. The limitations in understanding of disease biology, outcome measures, resources and barriers to trial participation in a rapidly progressive, disabling and heterogenous disease hindered timely and definitive evaluation of drugs in two-arm trials. Innovative trial designs, especially adaptive platform trials may offer significant efficiency gains to this end. We propose a flexible and scalable multi-arm, multi-stage trial platform where opportunities to participate in a clinical trial can become the default for people with amyotrophic lateral sclerosis.
Wong et al. reviewed historical approaches to clinical trials in amyotrophic lateral sclerosis. Lack of sensitive outcome measures, limitations in resources and barriers to trial participation were challenges for timely and definitive evaluation of drugs in two-arm trials. They concluded that future trials should be more flexible, scalable and efficient.
Graphical Abstract
Graphical Abstract
Satellite cells are the resident stem cell population of the adult mammalian skeletal muscle and they play a crucial role in its homeostasis and in its regenerative capacity after injury. We show ...here that the Polycomb group (PcG) gene Bmi1 is expressed in both the Pax7 positive (+)/Myf5 negative (-) stem cell population as well as the Pax7+/Myf5+ committed myogenic progenitor population. Depletion of Pax7+/Myf5- satellite cells with reciprocal increase in Pax7+/Myf5+ as well as MyoD positive (+) cells is seen in Bmi1-/- mice leading to reduced postnatal muscle fiber size and impaired regeneration upon injury. Bmi1-/- satellite cells have a reduced proliferative capacity and fail to re-enter the cell cycle when stimulated by high serum conditions in vitro, in keeping with a cell intrinsic defect. Thus, both the in vivo and in vitro results suggest that Bmi1 plays a crucial role in the maintenance of the stem cell pool in postnatal skeletal muscle and is essential for efficient muscle regeneration after injury especially after repeated muscle injury.
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