Biomarkers for amyotrophic lateral sclerosis
Purpose of review
Amyotrophic lateral sclerosis (ALS) is an incurable, devastating neurodegenerative disease. Still, the diagnosis is mainly based on clinical symptoms, and the treatment options are strongly limited. However, the pipeline of potential treatments currently tested in clinical trials is promising. This review will discuss developments in ALS biomarker research and applications within the last 2 years and suggest future directions and needs.
Recent findings
The diagnostic and prognostic utility of neurofilaments, a general marker for axoneuronal degeneration, has been confirmed by further studies in...
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: MOTOR NEURON DISEASE: Edited by Albert Ludolph Source Type: research
Progress in spinal muscular atrophy research
Purpose of review
The development of new therapies has brought spinal muscular atrophy (SMA) into the spotlight. However, this was preceded by a long journey – from the first clinical description to the discovery of the genetic cause to molecular mechanisms of RNA and DNA technology.
Recent findings
Since 2016, the antisense oligonucleotide nusinersen has been (FDA) approved for the treatment of SMA, followed by the gene replacement therapy onasemnogene abeparvovec-xioi in 2019 and the small-molecule risdiplam in 2020. These drugs, all targeting upregulation of the SMN protein not only showed remarkable effect...
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: MOTOR NEURON DISEASE: Edited by Albert Ludolph Source Type: research
Clinical studies in amyotrophic lateral sclerosis
This article focuses on studies, which provided either a positive primary endpoint or positive post hoc analysis, including edaravone, sodium phenylbutyrate–taurursodiol, rasagiline, tofersen, and high-caloric, fat-rich nutrition. It also covers recent developments in the design of clinical ALS studies with regard to inclusion criteria, stratification factors, and outcome parameters.
Summary
Recent clinical studies have indicated various substances to be considered for treatment of ALS. Edaravone has been approved by the US Food and Drug Association (FDA) but not by the European Medicines Agency (EMA), and further...
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: MOTOR NEURON DISEASE: Edited by Albert Ludolph Source Type: research
The challenge of amyotrophic lateral sclerosis descriptive epidemiology: to estimate low incidence rates across complex phenotypes in different geographic areas
Purpose of review
Amyotrophic lateral sclerosis (ALS) is a rare progressive neurodegenerative disease of motor neurons with a fatal outcome. The rareness of the disease and the rapidly fatal course are the main challenges for the ALS epidemiological research. The understanding of ALS has clearly advanced in the recent years both in the genetics and in the leading pathways of disease determinants. Epidemiological research has played a primary role in these discoveries.
Recent findings
Epidemiological studies have shown a variation of incidence, mortality and prevalence of ALS between geographical areas and differ...
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: MOTOR NEURON DISEASE: Edited by Albert Ludolph Source Type: research
Update on genetics of amyotrophic lateral sclerosis
Purpose of review
ALS genetics are highly dynamic and of great interest for the ALS research community. Each year, by using ever-growing datasets and cutting-edge methodology, an array of novel ALS-associated genes and downstream pathomechanisms are discovered. The increasing plenty and complexity of insights warrants regular summary by-reviews.
Recent findings
Most recent disease gene discoveries constitute the candidate and risk genes SPTLC1, KANK1, CAV1, HTT, and WDR7, as well as seven novel risk loci. Cell type and functional enrichment analyses enlighten the genetic basis of selective motor neuron vulnerabi...
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: MOTOR NEURON DISEASE: Edited by Albert Ludolph Source Type: research
Neuropathology and neuroanatomy of TDP-43 amyotrophic lateral sclerosis
Purpose of review
Intracellular inclusions consisting of the abnormal TDP-43 protein and its nucleocytoplasmic mislocalization in selected cell types are hallmark pathological features of sALS. Descriptive (histological, morphological), anatomical, and molecular studies all have improved our understanding of the neuropathology of sporadic amyotrophic lateral sclerosis (sALS). This review highlights some of the latest developments in the field.
Recent findings
Increasing evidence exists from experimental models for the prion-like nature of abnormal TDP-43, including a strain-effect, and with the help of neuroimag...
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: MOTOR NEURON DISEASE: Edited by Albert Ludolph Source Type: research
Editorial: Amyotrophic lateral sclerosis
No abstract available (Source: Current Opinion in Neurology)
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: MOTOR NEURON DISEASE: Edited by Albert Ludolph Source Type: research
Recent advances in our understanding of genetic rhabdomyolysis
Purpose of review
This review summarizes recent advances in our understanding of the genetics of rhabdomyolysis.
Recent findings
Rhabdomyolysis is the acute breakdown of myofibres resulting in systemic changes that can be life-threatening. Environmental triggers, including trauma, exercise, toxins and infections, and/or gene defects can precipitate rhabdomyolysis. A schema (aptly titled RHABDO) has been suggested for evaluating whether a patient with rhabdomyolysis is likely to harbour an underlying genetic defect. It is becoming increasingly recognized that defects in muscular dystrophy and myopathy genes can t...
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: MUSCULAR DISEASE: Edited by Ichizo Nishino Source Type: research
Therapeutic thoroughfares for adults living with Pompe disease
Purpose of review
Pompe disease is caused by autosomal recessive mutations in the acid α-glucosidase gene leading to a multiorgan deficiency of the enzyme acid glucosidase alfa. To recover to a nondiseased status, a lift over a threshold of 25% acid glucosidase alfa enzyme activity is required. This update on therapeutic thoroughfares for adult Pompe disease aims to assist neuromuscular and metabolic specialists.
Recent findings
We reviewed the recent studies covering enzyme replacement therapy, gene therapy, and substrate reduction therapy in adult Pompe disease. Results of phase 3 studies and the first sets o...
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: MUSCULAR DISEASE: Edited by Ichizo Nishino Source Type: research
Oculopharyngodistal myopathy
Purpose of review
Oculopharyngodistal myopathy (OPDM) is a rare adolescent or adult-onset neuromuscular disease that is characterized by progressive ocular, facial, pharyngeal and distal limb muscle weakness. The rimmed vacuoles and intranuclear inclusions in myofibers constitute the pathological hallmark of OPDM. In this review, the latest findings related to the genetic, molecular and clinical features of OPDM, as well as the diagnosis and management are summarized.
Recent findings
Four gene mutations, CGG repeats in the 5’-untranslated region of LRP12, GIPC1, NOTCH2NLC and RILPL1 have been reported to be di...
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: MUSCULAR DISEASE: Edited by Ichizo Nishino Source Type: research
Recent advances in establishing a cure for GNE myopathy
Purpose of review
GNE myopathy is a rare autosomal recessive disease caused by biallelic variants in the GNE gene, which encodes an enzyme involved in sialic acid biosynthesis. No drugs are approved for the treatment of GNE myopathy. Following proof-of-concept of sialic acid supplementation efficacy in mouse models, multiple clinical trials have been conducted. Here, we review clinical trials of sialic acid supplementation therapies and provide new insights into the additional clinical features of GNE myopathy.
Recent findings
Clinical trials of sialic acid supplementation have been conducted in Europe, the USA,...
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: MUSCULAR DISEASE: Edited by Ichizo Nishino Source Type: research
COVID-19 associated myopathy
Purpose of review
The global spread of severe acute respiratory syndrome coronavirus 2 resulted in many cases of acute and postacute muscular symptoms. In this review, we try to decipher the potential underlying pathomechanisms and summarize the potential links between viral infection and muscle affection.
Recent findings
Disregarding single case studies that do not allow safe conclusions due to the high number of infections, histopathological evidence of myositis has only been reported in deceased individuals with severe COVID-19. Postacute myalgia and weakness seem to occur in a subset of patients up to one ye...
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: MUSCULAR DISEASE: Edited by Ichizo Nishino Source Type: research
Update on dermatomyositis
Purpose of review
This review summarizes and comments on current knowledge in dermatomyositis.
Recent findings
The 2018 European Neuromuscular Centre classification of dermatomyositis has been challenging by the discovery of clinicopathological features associated with dermatomyositis-specific antibody (DMSA) that were not incorporated in the original criteria. These features include but may not be limited to the presence of perifascicular necrosis in anti-Mi-2 dermatomyositis; presence of diffuse nonperifascicular sarcoplasmic myxovirus resistance protein A expression in anti-MDA5 dermatomyositis; and dermatomy...
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: MUSCULAR DISEASE: Edited by Ichizo Nishino Source Type: research
Inclusion body myositis: evolving concepts
Purpose of review
To discuss recent developments in our understanding of epidemiology, diagnostics, biomarkers, pathology, pathogenesis, outcome measures, and therapeutics in inclusion body myositis (IBM).
Recent findings
Recent epidemiology data confirms a relatively higher prevalence in the population aged above 50 years and the reduced life expectancy. Association with cancer and other systemic disorders is better defined. The role of magnetic resonance imaging (MRI) and ultrasound in diagnosis as well as in following disease progression has been elucidated. There are new blood and imaging biomarkers that s...
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: MUSCULAR DISEASE: Edited by Ichizo Nishino Source Type: research
Autoimmune neuromyotonia
Purpose of review
Autoimmune neuromyotonia encompasses a group of rare immune-mediated neurological disorders frequently associated with anti-contactin-associated protein-like 2 (CASPR2) antibodies and featuring clinical and electrical signs of peripheral nerve hyperexcitability (PNH). We aim to summarize the current knowledge on immune-mediated neuromyotonia, focusing on clinical presentations, pathophysiology, and management.
Recent findings
Neuromyotonia is a major feature of several autoimmune neurological syndromes characterized by PNH with or without central neurological system involvement. Experimental an...
Source: Current Opinion in Neurology - September 13, 2022 Category: Neurology Tags: PERIPHERAL NERVE AND NEURO-MUSCULAR JUNCTION DISEASE: Edited by Luis Querol Source Type: research
