Current Opinion In Neurology[JOURNAL]
Sun
200 papers
The role of amino acid PET in the era of checkpoint inhibitors and targeted therapy for brain tumor treatment.
Galldiks N, Peplinski JM, Kraft M … +2 more , Lohmann P, Werner JM
Curr Opin Neurol · 2025 Dec · PMID 40802561 · Publisher ↗
PURPOSE OF REVIEW: To summarize the role of diagnostic amino acid PET in the era of checkpoint inhibitors and targeted therapies for brain tumor treatment. RECENT FINDINGS: Amino acid PET, particularly O -(2-[ 18 F]-fluo...
PURPOSE OF REVIEW: To summarize the role of diagnostic amino acid PET in the era of checkpoint inhibitors and targeted therapies for brain tumor treatment. RECENT FINDINGS: Amino acid PET, particularly O -(2-[ 18 F]-fluoroethyl)-L-tyrosine (FET) PET, has shown promise in distinguishing treatment-related changes such as pseudoprogression and pseudoresponse from true tumor relapse in patients receiving immunotherapy or targeted therapies for brain metastases and gliomas, often outperforming conventional MRI. Additionally, serial amino acid PET imaging has demonstrated potential in early response assessment following these agents. SUMMARY: Larger prospective trials with a higher number of patients are still needed to validate the clinical impact of amino acid PET when immunotherapy or targeted therapies are used for brain tumor therapy.
Amyotrophic lateral sclerosis in Mainland China: clinical translational challenges and opportunities.
He J, Fan D
Curr Opin Neurol · 2025 Oct · PMID 40772655 · Full text
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, therapeu...
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.
Neuroimaging endpoints for clinical trials in gliomas: the neuro-oncologist perspective.
Nakhate V, Youssef G, Lasica AB … +1 more , Wen PY
Curr Opin Neurol · 2025 Dec · PMID 40772641 · Publisher ↗
PURPOSE OF REVIEW: Accurate and reliable determination of tumor response and progression on neuroimaging is critical to identify effective therapies for glioma in clinical trials. In this article, we review response asse...
PURPOSE OF REVIEW: Accurate and reliable determination of tumor response and progression on neuroimaging is critical to identify effective therapies for glioma in clinical trials. In this article, we review response assessment criteria for adult glioma including their evolution over time, current recommendations, limitations, and future directions. RECENT FINDINGS: Response Assessment in Neuro-Oncology (RANO) 2.0 delineates unified magnetic resonance imaging (MRI)-based criteria informed by patient data to evaluate endpoints of tumor response and tumor progression. The positron emission tomography (PET) RANO 1.0 criteria propose endpoints for tumor progression and response on amino acid PET imaging. SUMMARY: The RANO 2.0 criteria provide standardized recommendations to assess tumor response and progression across adult glioma clinical trials regardless of tumor grade, contrast enhancement, molecular profile or treatment modality. Additional validation and exploratory studies can facilitate future refinements to the criteria and possible incorporation of novel neuroimaging endpoints. Advanced imaging modalities such as perfusion MRI and amino acid PET may help overcome some limitations of MRI-based response assessment.
Small fiber neuropathy: expanding diagnosis with unsettled etiology.
Devigili G, Marchi M, Lauria G
Curr Opin Neurol · 2025 Oct · PMID 40772640 · Full text
PURPOSE OF REVIEW: Small fiber neuropathies (SFN) are a heterogeneous group of disorders affecting the thinly myelinated Aδ and unmyelinated C-fibers. The clinical picture is dominated by neuropathic pain, often accompan...
PURPOSE OF REVIEW: Small fiber neuropathies (SFN) are a heterogeneous group of disorders affecting the thinly myelinated Aδ and unmyelinated C-fibers. The clinical picture is dominated by neuropathic pain, often accompanied by autonomic symptoms of variable severity. The underlying causes encompass metabolic conditions like diabetes mellitus, immuno-mediated disorders, infection, exposure to toxins, and gain-of-function variants in the genes encoding the Nav1.7, Nav1.8, and Nav1.9 sodium channel subunits, though the list of associated diseases continues to grow. Recently, increased attention has focused on immune-mediated forms, which led to the identification of potentially treatable subgroups. These discoveries have advanced our understanding of pathophysiological mechanisms. RECENT FINDINGS: Recent studies have broadened the spectrum of underlying conditions associated with SFN, including immune-mediated forms and links to SARS-CoV-2 infection and vaccines. Studies on genetic variants linked to unique clinical presentations have also yielded new insights. Furthermore, emerging perspectives highlighted disorders involving small fiber pathology that lacks typical clinical features of neuropathic pain, challenging traditional diagnostic criteria. SUMMARY: Deepening our understanding of the causes underlying SFN advances the identification of potential therapeutic targets. The clinical presentation of SFN can vary significantly and may not consistently correlate with specific underlying conditions. Therefore, a systematic investigation of possible causes through a structured diagnostic assessment is critical to unveil additional contributing factors.
Genetics of ALS - genes and modifier.
Menge S, Decker L, Freischmidt A
Curr Opin Neurol · 2025 Oct · PMID 40772638 · Full text
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 progre...
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.
Is amyotrophic lateral sclerosis less severe in mice than in humans?
Dupuis L, Robertson J
Curr Opin Neurol · 2025 Oct · PMID 40767546 · Publisher ↗
PURPOSE OF REVIEW: We review here novel knock-in models of amyotrophic lateral sclerosis (ALS). RECENT FINDINGS: Knock-in mouse models of various familial forms of ALS generally display a mild motor phenotype, with limit...
PURPOSE OF REVIEW: We review here novel knock-in models of amyotrophic lateral sclerosis (ALS). RECENT FINDINGS: Knock-in mouse models of various familial forms of ALS generally display a mild motor phenotype, with limited progression, that do not recapitulate the full-blown clinical picture of ALS. SUMMARY: ALS is a devastating neurodegenerative disease in humans. Typically manifesting in the fifth or sixth decade of life, ALS leads to progressive motor dysfunction and death, usually within 2-5 years from symptom onset. A subset of ALS cases are dominantly inherited. Over the last 30 years, multiple mouse models of ALS have been generated, and recent advances in mouse genome editing techniques have enabled the generation of mouse strains carrying orthologous mutations in endogenous genes that mirror those causing familial forms of ALS. Intriguingly, many of these knock-in mouse models develop much milder phenotypes than patients with ALS carrying the same mutations. A full-blown ALS clinical phenotype seems to be only elicited upon overexpression of mutant genes beyond the endogenous levels. Here, we review these novel models and argue that these models could represent how ALS manifests in the mouse species. We also evaluate how these models could be used for characterizing mechanisms and preclinical drug evaluation.
New insights in the immune treatment of Guillain-Barré syndrome.
Wiegers EJA, Jacobs BC
Curr Opin Neurol · 2025 Oct · PMID 40748027 · Full text
PURPOSE OF REVIEW: Guillain-Barré syndrome (GBS) is a severe but treatable form of immune-mediated neuropathy. The purpose of this review is to provide an update on current immune treatments for GBS, highlight challenges...
PURPOSE OF REVIEW: Guillain-Barré syndrome (GBS) is a severe but treatable form of immune-mediated neuropathy. The purpose of this review is to provide an update on current immune treatments for GBS, highlight challenges in clinical practice and research, and discuss new developments in therapies that focus on reducing inflammation and preventing further nerve damage. RECENT FINDINGS: In 2023, a GRADE-based guideline was published on the diagnosis and treatment of GBS on behalf of EAN/PNS. Several clinical trials have been conducted in GBS recently, including studies with an observational comparative study design. SUMMARY: Since 30 years, intravenous immunoglobulins and plasma exchange are the only proven effective immune treatments for GBS. Despite these treatments, a substantial proportion of patients recover incompletely and have residual disability or complaints with a high impact on quality of life. New treatment trials focus on reducing immunoglobulin G antibodies to nerves and inhibition of complement activation. Observational comparative studies based on extensive and well defined cohorts are an alternative method to evaluate the effect of treatments in GBS. Several novel study designs are discussed that aim to facilitate the conduct of future trials with more sustainable use of data.
Controversies in the diagnosis of chronic inflammatory demyelinating polyneuropathy.
Doneddu PE, Fasano C, Lozi C … +2 more , Marenna G, Nobile-Orazio E
Curr Opin Neurol · 2025 Oct · PMID 40748018 · Full text
PURPOSE OF REVIEW: Despite decades of clinical recognition, the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) remains fraught with uncertainty. This review examines major areas of ongoing...
PURPOSE OF REVIEW: Despite decades of clinical recognition, the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) remains fraught with uncertainty. This review examines major areas of ongoing controversy in the diagnostic evaluation of CIDP, focusing on recent changes to electrodiagnostic criteria, disease boundaries, and emerging concepts of axonal damage. RECENT FINDINGS: Recent literature highlights three key areas of diagnostic uncertainty: the evolution and limitations of electrodiagnostic criteria; the diagnostic boundary between CIDP and antimyelin-associated glycoprotein (anti-MAG0 antibody neuropathy; and the recognition of CIDP cases that do not fulfil electrodiagnostic criteria, raising interest in axonal variants and the potential role of biomarkers such as neurofilaments. Across these domains, discrepancies between empirical evidence and expert-based guidelines persist, contributing to misdiagnosis and treatment variability. SUMMARY: Current CIDP criteria, though improved, remain partly based on expert opinion rather than empirical validation. The clinical heterogeneity of CIDP and its overlap with mimicking disorders further complicate diagnosis. A broader, more flexible diagnostic framework - integrating electrophysiology, biomarkers, and treatment response - is essential to enhance diagnostic accuracy and guide therapy. Future research should focus on refining criteria to strengthen electrodiagnostic standards and better accommodate atypical and axonal presentations.
Neurotoxicity from chimeric antigen receptor T-cells: an update on diagnosis and treatment.
Ursu R, Cuzzubbo S, Carpentier AF
Curr Opin Neurol · 2025 Dec · PMID 40748015 · Publisher ↗
PURPOSE OF REVIEW: Chimeric antigen receptor (CAR) T-cell therapies are increasingly used in hematologic malignancies and are now being investigated in autoimmune disorders. This review aims to summarize the spectrum of...
PURPOSE OF REVIEW: Chimeric antigen receptor (CAR) T-cell therapies are increasingly used in hematologic malignancies and are now being investigated in autoimmune disorders. This review aims to summarize the spectrum of neurological complications associated with CAR-T. RECENT FINDINGS: While early-onset neurotoxicity is well characterized, other neurological syndromes are increasingly reported. Neurological complications can be provisionally classified into three categories: early-onset immune effector cell-associated neurotoxicity syndrome (ICANS); delayed-onset neurological syndromes specific to single CAR T-cell types; and tumour inflammation-associated neurotoxicity (TIAN). Other postinfusion neurological syndromes have also been observed but with uncertain links to CAR T-cells. Management must be tailored to preserve both neurological function and CAR T-cell efficacy. Ongoing efforts target biomarker development, and risk-adapted strategies, especially in steroid-refractory cases. SUMMARY: As CAR T-cell indications broaden, clinicians must recognize diverse neurological toxicities and implement individualized, evidence-based interventions to improve neurological outcomes.
Neurosyphilis in 2025.
Sethi V, Marks M
Curr Opin Neurol · 2025 Aug · PMID 40605685 · Publisher ↗
PURPOSE OF REVIEW: Syphilis continues to be a major global health problem. In recent years epidemics of syphilis have also been reported in many high-income countries. In this review, we aim to highlight varied presentat...
PURPOSE OF REVIEW: Syphilis continues to be a major global health problem. In recent years epidemics of syphilis have also been reported in many high-income countries. In this review, we aim to highlight varied presentations, including recent guidelines on diagnosis and treatment, including in people with HIV (PWH). RECENT FINDINGS: Neurosyphilis is increasingly being diagnosed and presentations are varied in both the immunocompetent and immunocompromised host. An appropriate history, examination and diagnostic work-up is central to identification of neurosyphilis and to enable appropriate treatment. Clear criteria for indication and interpretation of results from lumbar punctures, neuroimaging and treatment protocols have been outlined by the British association for sexual health and HIV (BASHH) in 2024. SUMMARY: The increase in overall cases of syphilis has been accompanied by increases in the number of cases with neurological involvement. The presentation of neurosyphilis is variable and may occur early or late in the disease course. It is important to be aware of the varied presentations, diagnostic and treatment criteria to limit the late sequelae of disease and address the global health challenge it poses and measures being taken to help reduce this global burden.
Neurocysticercosis: current diagnostic and treatment paradigms.
Singh G, Chomba M, Sander JW
Curr Opin Neurol · 2025 Aug · PMID 40605684 · Publisher ↗
PURPOSE OF REVIEW: Neurocysticercosis, the infestation of the human central nervous system by Taenia solium cysts, accounts for a significant burden of neurological disorders in endemic regions. It is a neglected tropica...
PURPOSE OF REVIEW: Neurocysticercosis, the infestation of the human central nervous system by Taenia solium cysts, accounts for a significant burden of neurological disorders in endemic regions. It is a neglected tropical disease and, hence, often overlooked. However, its importance is underscored by the high burden of epilepsy in endemic regions and many imported cases in nonendemic areas. Given recent epidemiological shifts and advances in diagnosis and treatment, a new focus on neurocysticercosis is required. RECENT FINDINGS: While South & Central America remain endemic, sub-Saharan Africa has emerged as a newly recognized hotspot. Recent developments include the potential for antigen-based assays to facilitate 'point of care' diagnosis and treatment monitoring, the combination of antiparasitic regimens, and a newer antiparasitic agent, oxfendazole, currently in clinical trial. SUMMARY: Recent developments offer significant hope. Wider access to neuroimaging, improved serological tests including antigen assays, and novel therapeutic strategies such as combination antiparasitic treatment have improved outcomes. Ultimately, however, a concerted prevention strategy incorporating diverse approaches will be crucial in reducing the global burden of neurological disorders associated with neurocysticercosis.
Neuro-infectious disorders - reasons to be cheerful but it is a long and winding road.
Manji H
Curr Opin Neurol · 2025 Aug · PMID 40605683 · Publisher ↗
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Biomarkers in inflammatory neuropathies: where are we?
Michael MR, Wieske L, Eftimov F
Curr Opin Neurol · 2025 Oct · PMID 40504073 · Publisher ↗
PURPOSE OF REVIEW: This review provides an overview of recent advances in fluid-based biomarker research in inflammatory neuropathies, with a particular focus on disease activity monitoring. It explores challenges along...
PURPOSE OF REVIEW: This review provides an overview of recent advances in fluid-based biomarker research in inflammatory neuropathies, with a particular focus on disease activity monitoring. It explores challenges along the biomarker pipeline and outlines the stage of development of emerging disease activity biomarkers. RECENT FINDINGS: Numerous biomarkers have recently been investigated for diagnostic, prognostic and monitoring purposes. Neurofilament light chain has been studied furthest but its clinical utility is limited in most patients. Other recent work has identified new biomarkers reflecting nerve damage, including peripherin, periaxin and Contactin-1. Additionally, potential immunological markers of disease activity have been explored, some more generic (such as chemokines) and others highly disease specific (such as autoantibody titers). Additional candidates have emerged through unbiased high-throughput discovery studies. SUMMARY: Current fluid-based biomarkers can be grouped into nerve damage or immunological biomarkers. Most have not proceeded beyond discovery and validation stages, except for Neurofilament Light Chain. Biomarker development is challenging due to the inherent rarity and heterogeneity of inflammatory neuropathies, and, in the case of disease activity biomarkers, a lack of reference standard.
Emerging neuroinfectious diseases: public health implications.
Kim CY, Holroyd KB, Thakur KT
Curr Opin Neurol · 2025 Aug · PMID 40501312 · Publisher ↗
PURPOSE OF REVIEW: Direct neurological consequences from emerging and re-emerging infectious diseases such as poliomyelitis, West Nile virus and Zika virus, and those with indirect neurological effects such as COVID-19 a...
PURPOSE OF REVIEW: Direct neurological consequences from emerging and re-emerging infectious diseases such as poliomyelitis, West Nile virus and Zika virus, and those with indirect neurological effects such as COVID-19 and Influenza, are major contributors to the profound impact of infectious diseases on global human health. Here, we highlight select infections of the nervous system of public health significance and discuss some of the key factors of emergence. We focus on vector-borne infections including Oropouche virus and West Nile virus, those transmitted by other nonvector animal species including Nipah and Hendra virus, and vaccine preventable infections including neurological effects of Measles virus. RECENT FINDINGS: Currently, the emergence of Oropouche virus, Avian Influenza, and the re-emergence of Measles outbreaks across Europe and America, are examples of current emerging infectious disease outbreaks. As pathogens spread to new areas, we will continue to see a rise in populations at risk of severe neurological effects. The recent resurgence of measles virus cases exemplifies the importance of strong vaccination programs and preventive public health measures to mitigate the impact of preventable re-emerging infections in vulnerable populations. SUMMARY: Neuroinfectious diseases will continue to drive significant morbidity and mortality on global populations as risk factors remain high, and global public health initiatives are hampered by inadequate governmental support.
Update on statin-associated myopathy symptoms in the view of new clinical management strategies.
Musumeci O, Drago SFA
Curr Opin Neurol · 2025 Oct · PMID 40501310 · Publisher ↗
PURPOSE OF REVIEW: Purpose of this review is to highlight the recent findings in terms of clinical aspects, pathogenic mechanisms and managements of statin associated muscle symptoms (SAMS), and focusing on the use of no...
PURPOSE OF REVIEW: Purpose of this review is to highlight the recent findings in terms of clinical aspects, pathogenic mechanisms and managements of statin associated muscle symptoms (SAMS), and focusing on the use of novel therapeutic alternatives in clinical practice. RECENT FINDINGS: While extensive research has been conducted on SAMS, the precise mechanisms remain unclear. Recent findings continue to explore various aspects, including potential risk factors, diagnostic approaches, and management strategies. Managing SAMS involves a careful assessment to confirm the diagnosis, a stepwise approach to treatment that may include dose adjustments, switching statins, considering alternate-day dosing, and exploring nonstatin therapies, all while prioritizing patient well being and cardiovascular risk reduction through shared decision-making and ongoing monitoring. In recent years, the therapeutic landscape has expanded with the introduction of several novel lipid-lowering agents, providing valuable alternatives for both statin-tolerant and statin-intolerant patients but their use in clinical practice is still limited because of high costs, regulatory limitations and type of administration. SUMMARY: Given the increasing use of both traditional and emerging lipid-lowering therapies, a clear understanding of their comparative safety, particularly regarding musculoskeletal adverse effects, is essential for guiding clinical decision-making.
Nerve ultrasound in the diagnosis of inflammatory neuropathies.
Leonardi L, Cerantola E, Salvalaggio A
Curr Opin Neurol · 2025 Oct · PMID 40501305 · Publisher ↗
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), multifo...
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.
Current understanding of skeletal muscle repeat expansion disorders.
Boivin M, Ravenscroft G
Curr Opin Neurol · 2025 Oct · PMID 40488265 · Publisher ↗
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 genom...
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.
Myofibrillar myopathy: towards a mechanism-based definition as a Z-disk-opathy.
Inoue M, Weihl CC
Curr Opin Neurol · 2025 Oct · PMID 40488240 · Full text
PURPOSE OF REVIEW: Myofibrillar myopathies (MFMs) are traditionally defined by histopathology, but recent genetic discoveries have broadened the spectrum of causative genes beyond Z-disk components. This review aims to a...
PURPOSE OF REVIEW: Myofibrillar myopathies (MFMs) are traditionally defined by histopathology, but recent genetic discoveries have broadened the spectrum of causative genes beyond Z-disk components. This review aims to address the resulting terminological inconsistency by proposing a refined, mechanism-based definition of MFM centered on its identity as a "Z-disk-opathy." This re-evaluation is timely and relevant for improving diagnostic clarity and guiding future research. RECENT FINDINGS: The literature increasingly reports MFM-like pathology in conditions caused by mutations in genes not directly encoding Z-disk structural proteins or their interacting chaperones. This review highlights the pathogenic mechanisms distinguishing true MFMs, which involve disruption of Z-disk protein structure or Z-disk protein homeostasis, from "myopathies with MFM pathology" that share histological features but stem from different molecular etiologies. Key themes include the dominant nature of mutations in Z-disk structural proteins and the critical role of chaperone dysfunction in MFM pathogenesis. SUMMARY: A refined definition classifying MFM as a "Z-disk-opathy" offers a clearer framework for diagnosis and mechanistic understanding. This distinction has significant implications for clinical practice, facilitating more accurate diagnosis, and for research, by supporting the development of targeted therapeutic strategies aimed at either restoring Z-disk proteostasis or mitigating the effects of aberrant protein accumulation.
The impact of climate change on neuroinfectious diseases.
Jacinto S
Curr Opin Neurol · 2025 Aug · PMID 40471846 · Publisher ↗
PURPOSE OF REVIEW: COP28 Health Day demonstrated the growing global attention to climate health. The purpose of this article is to review the impact of climate change on the emergence of neuro-infectious diseases. RECENT...
PURPOSE OF REVIEW: COP28 Health Day demonstrated the growing global attention to climate health. The purpose of this article is to review the impact of climate change on the emergence of neuro-infectious diseases. RECENT FINDINGS: Climate change influences meteorological shifts and extreme weather events which may have significant and complex effects on the emergence of neuroinfectious diseases. Particularly concerning is increasing vector borne, water borne and food borne diseases. Climate associated factors contribute to the high incidence of bacterial meningitis in the African Meningitis Belt, and expansion of viral and fungal meningitis in other regions. Increased risks to those living with HIV is a public health concern. The most vulnerable communities, especially in low and middle-income countries, will be particularly impacted. SUMMARY: The complex effects of climate change on the emergence of neuroinfectious diseases result from consequences on ecologies, populations and health systems. The growing health burden must be addressed with a multifaceted approach to establishing climate resilient healthcare systems.
Chronic idiopathic axonal neuropathy: antibodies, genetics, and beyond.
Sari MC, Hoke A
Curr Opin Neurol · 2025 Oct · PMID 40471691 · Publisher ↗
PURPOSE OF REVIEW: Chronic idiopathic axonal neuropathy (CIAP) remains a diagnostic challenge, with many cases historically classified as idiopathic due to the absence of identifiable genetic, metabolic, or immune-mediat...
PURPOSE OF REVIEW: Chronic idiopathic axonal neuropathy (CIAP) remains a diagnostic challenge, with many cases historically classified as idiopathic due to the absence of identifiable genetic, metabolic, or immune-mediated causes. This review examines recent advancements in understanding CIAP, focusing on novel genetic mutations, autoantibodies, and metabolic pathways that challenge the "idiopathic" designation. Specifically, we highlight sorbitol dehydrogenase (SORD) deficiency and replication factor C subunit 1 (RFC1) repeat expansions, and comment on the controversy surrounding autoantibody-associated small fiber neuropathy (SFN). RECENT FINDINGS: Biallelic SORD mutations have emerged as a leading cause of recessive axonal neuropathy, linked to sorbitol accumulation and neurotoxicity, with aldose reductase inhibitors (ARIs) being explored as a potential therapy. RFC1 intronic repeat expansions have been identified as a major genetic contributor to CANVAS and sensory neuropathies, reshaping diagnostic approaches for patients previously classified as idiopathic. Additionally, the identification of autoantibodies such as trisulfated heparin disaccharide (TS-HDS), fibroblast growth factor receptor 3 (FGFR-3), and Plexin D1 in SFN suggests an immune-mediated pathology in a subset of patients but a negative randomized trial of IVIG and lack of specificity of TS-HDS IgM antibody testing questions the relevance of these presumed autoantibodies. SUMMARY: Advances in genetics, immunology, and metabolic neuropathies are redefining CIAP. The identification of SORD deficiency, RFC1 expansions, and autoantibody-associated SFN highlights the need for biomarker-driven approaches and targeted therapies. Future research should focus on expanding genetic screening, optimizing immunotherapy strategies, and investigating novel metabolic contributors to CIAP, ultimately moving toward precise, mechanism-based diagnoses.
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