Current Opinion in Neurology最新文献

Purpose of review: This review synthesizes the recent advances in the application of nerve ultrasound (US) to inflammatory neuropathies, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), Guillain-Barré syndrome (GBS), neuralgic amyotrophy (NA), Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes syndrome (POEMS), and anti-MAG neuropathy. The aim is to clarify nerve US clinical utility and guide its use in clinical practice.

Recent findings: Nerve US supports differential diagnosis through characteristic sonographic patterns. In CIDP, it aids in identifying atypical forms, predicting treatment response, and may have a role in follow-up. In MMN, nerve US shows diagnostic value. In GBS, it can help differentiate acute-onset CIDP. In NA, alterations can be detected within hours from the onset. Anti-MAG antibody neuropathy lacks well characterized US features. In POEMS and vasculitis, data are scarce and conflicting.

Summary: Nerve US is an established tool for diagnosing neuropathies, as it is noninvasive, accessible, reproducible, and complements electrophysiology. Its role is established in CIDP and its variants, while evidence supports its utility in MMN and the differential diagnosis of neuropathies with an inflammatory-like clinical presentation. In NA, nerve US may outperform neurophysiology. It appears less useful in GBS, POEMS, and anti-MAG neuropathy.

Purpose of review: Myotonic dystrophy type 1 (DM1) is a genetically mediated, multisystemic neuromuscular disorder with significant phenotypic heterogeneity. This review aimed to summarize recent advances in clinical understanding, natural history, and therapeutic development, with a focus on cardiac, respiratory, cognitive, and pediatric aspects of DM1.

Recent findings: Longitudinal studies are refining the natural history of both adult and pediatric DM1. Advances in biomarker discovery, including composite ribosomal nucleic acid splicing metrics and imaging findings, are improving disease monitoring and treatment assessment. Cardiac risk stratification is evolving, although respiratory management remains challenging due to adherence issues. Increasing attention is being given to cognitive and behavioral impairments, particularly in congenital and childhood-onset DM1. Although disease-modifying therapies remain in development, real-world data on symptomatic treatments such as mexiletine and nonpharmacological interventions, including exercise and cognitive behavioral therapy, provide valuable clinical insights.

Summary: Recent literature highlights substantial progress in understanding DM1 across different age groups and organ systems. Although no approved disease-modifying therapies exist, ongoing clinical trials and biomarker advancements offer hope. This review synthesizes these developments to inform clinical management and guide future research efforts.

Purpose of review: Here, we summarize the current knowledge about the genetics and proposed mechanisms of disease underlying skeletal muscle short tandem repeat (STR) expansion disorders.

Recent findings: The human genome contains up to 2 million STRs (also known as microsatellites), which are highly variable repetitions of two to six nucleotide-long DNA motifs. These elements, present in both coding and noncoding sequences, are highly instable, and their polymorphic variations have important roles in genes regulation and human phenotypic trait diversity. Importantly, expansion over a threshold size of a subset of these STR is the cause of approximately 60 neurological diseases, including some major muscle disorders such as myotonic dystrophy, oculopharyngodistal myopathy (OPDM) and oculopharyngeal muscular dystrophy. The discovery and characterisation of a number of these STR expansion disorders, in particular for OPDM, has been enabled in recent years by advanced genomic technologies.

Summary: Many recently described STR expansion disorders are now recognized and genetic testing of patients is possible on a research basis, clinical testing for these newly described repeat loci is not yet readily available and is complicated by the reduced penetrance seen in some families, rendering clinical interpretation more difficult. The phenotypic spectrums associated with these STR expansion disorders are also evolving as unbiased sequencing approaches identified expansions at known loci in individuals with phenotypes that are quite different to those in which the STR expansions were first characterized. The pathomechanisms associated with these newer STR expansion disorders is still poorly understood, however there is evidence of both RNA toxicity and polyGly toxicity. Additional STR expansions underlying skeletal muscle diseases are likely to be identified in coming years and may shed further light onto the complex genetics, epigenetics and disease mechanisms underlying these disorders.

Purpose of review: Amyotrophic lateral sclerosis (ALS) imposes a growing medical and socioeconomic burden in China. This review synthesizes recent advances in understanding ALS epidemiology, biomarker discovery, therapeutic innovations, and policy frameworks in China. It highlights the urgency of addressing challenges, including fragmented healthcare resources, translational medicine gaps, and regional inequities, while emphasizing China's unique contributions to global ALS research.

Recent findings: Chinese ALS cohorts exhibit distinct epidemiological profiles, including a younger mean age of onset and prolonged median survival. Policy initiatives, such as ALS inclusion in rare disease registries and insurance reforms, aim to reduce financial burdens of patients. Multimodal biomarker exploration has advanced integrated diagnostic models combining neurofilament light chain (NfL) and clinical data platforms. Neuroimaging and electrophysiological studies reveal glymphatic dysfunction, white matter degeneration, and neuromuscular junction abnormalities, with novel links to hepatic metabolism. Genomic analyses identify population-specific variants. Therapeutic innovations in China include not only biopharmaceuticals, but also integrative traditional Chinese medicine (TCM) approaches.

Summary: China's ALS landscape is transitioning towards precision medicine through biomarker-guided diagnostics and multidisciplinary care models. Key priorities include establishing a national ALS registry, standardizing biomarker validation, and expanding clinical trials to bridge translational medicine gaps.

Purpose of review: Amyotrophic lateral sclerosis (ALS) is a complex genetic disorder, and the pace of discoveries is very rapid. This review aims at briefly summarizing our current knowledge, and at discussing the progress of the last two years.

Recent findings: Common variation in numerous genes and variants in some nuclear-encoded mitochondrial genes were linked to an increased or modified risk of ALS, respectively. Mitochondrial function, i.e. specific mitochondrial haplotypes and loss-of-function variants in mitochondria-related genes, was identified as potent modifier of ALS survival, but not risk. Pioneering analyses of copy number variations in ALS-related genes revealed an increased load in ALS, but causality is unclear. A rare hyperactive variant of ER stress associated transcription factor CREB3 was linked to both substantially decreased ALS risk and slower disease progression. Furthermore, variants in IGFBP7 were linked to rare "ALS reversals", but existence of such phenotypes is controversial.

Summary: Common variation increasing ALS risk contributes to our understanding of sporadic ALS, and novel structural variants have the potential to at least partly explain the missing heritability in ALS. Identification of mitochondrial function and ER stress signaling as potent disease modifiers provide valuable starting points for therapeutic approaches beyond targeting single causative genes.

Purpose of review: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with few treatment options available. The approval of tofersen, an antisense oligonucleotide, for SOD1 -ALS by the FDA and EMA may herald a new era of treatment in these patients.

Recent findings: So far, trials against the most common genetic form of ALS, C9orf72 , have been unsuccessful, but new preclinical data may show a promising new direction to take. Clinical trials targeting other, more rare genetic mutations associated with familial ALS are currently underway. Other research assessing the use of ASOs to target aberrant splicing associated with sporadic forms of ALS has also produced promising results in preclinical models, using patient-derived induced cellular models and animal models. These therapies are focussed largely on alleviating and reversing TDP-43 pathology, opening up the possibility of not only arresting disease progression, but reversing neurodegeneration.

Summary: ASO therapies have made some promising steps towards treating familial ALS, particularly SOD1 . Ongoing early clinical/preclinical phase research is underway to utilise this technology in other genetic mutations linked with ALS, as well as in sporadic cases.

Purpose of review: Although inclusion body myositis (IBM) is considered a rare disease, it is the most prevalent inflammatory myopathy in adults over 50 years of age. Its complex pathophysiological background includes inflammatory and degenerative features, but it remains poorly understood. As a result, no effective therapy is currently available. In this review, we provide an update on the relevant contemporary literature addressing the clinical and pathophysiological aspects of IBM.

Recent findings: Recent studies have investigated drugs for IBM, including the immunosuppressant sirolimus, but haven't shown satisfactory results. Some advancements have been made in investigating IBM pathophysiology: a cell culture model recapitulating key disease features has been established. Multiple studies have used RNA sequencing to elucidate disease-specific pathways, including selective type 2 fiber vulnerability. The importance of TDP-43 deposition and subsequent mis-splicing as a disease mechanism has been demonstrated. Further studies have shown the value of patient-reported outcome measures (PROM) and quantitative MRI as investigation tools. Research has also investigated and demonstrated the complex genetic susceptibility related to IBM.

Summary: In conclusion, significant discoveries have been made in the past year that enhance our clinical and pathophysiological insights into IBM. Due to the persistent lack of effective therapeutic options, additional research is essential - not only to investigate potential treatments but also to reveal the disease's underlying mechanisms.