Current Opinion In Neurology[JOURNAL]
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200 papers
Deep brain stimulation of the mesencephalic locomotor region or lateral hypothalamus for facilitation of walking after spinal cord injury.
Noga BR, Serville J, Guest JD
Curr Opin Neurol · 2025 Dec · PMID 41189509 · Publisher ↗
PURPOSE OF REVIEW: Spinal cord injury (SCI) causes profound gait impairment and autonomic dysfunction. Deep brain stimulation (DBS) of supraspinal locomotor centers may strengthen spared descending motor and autonomic pa...
PURPOSE OF REVIEW: Spinal cord injury (SCI) causes profound gait impairment and autonomic dysfunction. Deep brain stimulation (DBS) of supraspinal locomotor centers may strengthen spared descending motor and autonomic pathways to improve walking. Preclinical and clinical studies have targeted the cuneiform nucleus (CnF) and pedunculopontine nucleus (PPN) of the mesencephalic locomotor region (MLR) and the lateral hypothalamus. To summarize recent progress in DBS as a strategy to facilitate locomotion with a particular focus on SCI. RECENT FINDINGS: DBS of the CnF, PPN, and lateral hypothalamus enhances gait and cardiorespiratory function in animal models and early human trials. Directional electrodes and individualized programming appear to reduce risks and optimize efficacy. Evidence suggests DBS can amplify supraspinal command circuits, supporting locomotor facilitation after injury. SUMMARY: DBS of MLR and lateral hypothalamus circuits represent a promising therapeutic approach for gait recovery in SCI. Key priorities for future clinical trials include stratification by injury severity, monitoring of autonomic outcomes, and assessment of long-term effects on mobility and quality of life. Integration with physiotherapy may further augment recovery. Collectively, current findings support DBS as an emerging intervention to restore locomotor function following SCI. The use of DBS for motor recovery after SCI is investigational.
Toward convergence in spinal cord injury therapies: neuromodulation, pharmacology, imaging, and rehabilitation.
Guest J, Bloom O
Curr Opin Neurol · 2025 Dec · PMID 41189508 · Publisher ↗
Abstract loading — click title to view on PubMed.
Advances in imaging analysis of the inner ear in patients with Meniere's disease.
Sone M, Yoshida T, Naganawa S
Curr Opin Neurol · 2026 Feb · PMID 41186090 · Publisher ↗
PURPOSE OF REVIEW: Visualization of endolymphatic hydrops using MRI has become a cutting-edge method not only for diagnosing Meniere's disease but also for pathophysiological elucidation of the disease. Here, we review r...
PURPOSE OF REVIEW: Visualization of endolymphatic hydrops using MRI has become a cutting-edge method not only for diagnosing Meniere's disease but also for pathophysiological elucidation of the disease. Here, we review recent advances in imaging analysis of the inner ear in Meniere's disease, which could provide additional information over previous findings. RECENT FINDINGS: In addition to identification of endolymphatic hydrops on MRI, high-intensity signals in the perilymph, which represent alterations in vascular permeability in the blood-perilymph barrier (BPB), might be a key to elucidating the pathophysiology of Meniere's disease. Moreover, high-intensity signals in the endolymphatic duct, which indicate disturbances of the lymph-capillary system, might provide new information for elucidating the pathogenesis of hearing loss and dizziness/vertigo not associated with endolymphatic hydrops. SUMMARY: Presence of endolymphatic hydrops is not necessarily the cause of symptoms related to Meniere's disease. Alteration of the BLB might lead to additional disturbances in ears with Meniere's disease and induce clinical symptoms. Disturbances of the lymph-capillary system in endolymphatic duct might induce audio-vestibular symptoms in ears without endolymphatic hydrops. Further development of MRI evaluation of inner ear conditions is desirable not only for accurate diagnosis and elucidation of the pathophysiology of the diseases, but also for early medical intervention to prevent their progression.
Kunming Locomotor Training: neurological, functional, and autonomic outcomes in complete spinal cord injury.
Zhu H, So KF, Feng X … +2 more , Niu F, Guest JD
Curr Opin Neurol · 2025 Dec · PMID 41143726 · Full text
PURPOSE OF REVIEW: Recovery after spinal cord injury (SCI) is variable, and the contribution of locomotor training to neurological and functional outcomes remains debated. This review summarizes post-SCI locomotor recove...
PURPOSE OF REVIEW: Recovery after spinal cord injury (SCI) is variable, and the contribution of locomotor training to neurological and functional outcomes remains debated. This review summarizes post-SCI locomotor recovery patterns, compares training modalities, and presents recovery findings from the Kunming Locomotor Training (KLT) program, one of the largest reported series of patients with initial complete (AIS A) injuries. RECENT FINDINGS: Several months of intensive task-specific overground training yielded substantial gains in neurological, locomotor, and autonomic outcomes. In a retrospective cohort of 485 AIS A patients, 47% improved their AIS grade, while nearly all showed some locomotor recovery measured by the Kunming Locomotor Scale (KLS). A ≥4-point KLS gain strongly predicted AIS conversion (sensitivity 83%, specificity 82%). Recovery probability was highest with lower thoracic and lumbar injuries. Improvements, including ambulation with assistive devices, and significant bladder and bowel recovery occurred even without AIS change. These outcomes reinforce the importance of active, patient-driven training. SUMMARY: KLT experience indicates that prolonged, intensive overground locomotor training can promote neurological and functional recovery in individuals with initially complete injuries. KLS provides a sensitive measure of functional progress. These findings underscore the clinical value of task-specific stepping and provide a new benchmark for evaluating sustained rehabilitation strategies and research into post-SCI recovery.
Riluzole as a pharmacological therapy for spinal cord injury: where does this therapy stand?
Pedro KM, Alvi MA, Goulart GR … +1 more , Fehlings MG
Curr Opin Neurol · 2025 Dec · PMID 41117139 · Publisher ↗
PURPOSE OF REVIEW: Spinal cord injury (SCI) remains a disabling condition associated with long term neurological impairment, functional disability, and reduced quality of life. Despite decades of research, pharmacologica...
PURPOSE OF REVIEW: Spinal cord injury (SCI) remains a disabling condition associated with long term neurological impairment, functional disability, and reduced quality of life. Despite decades of research, pharmacological interventions with proven clinical efficacy remain limited. This review critically evaluates the current evidence supporting riluzole as a neuroprotective agent for acute traumatic and nontraumatic SCI. We synthesize findings from preclinical and clinical studies, assess the progress towards clinical translation, and outline key challenges and research opportunities for future implementation. RECENT FINDINGS: Riluzole, an FDA-approved agent for amyotrophic lateral sclerosis (ALS), inhibits voltage-gated sodium channels and modulates glutaminergic transmission, two mechanisms central to the pathogenesis of secondary injury in SCI and in nerve cell degeneration in nontraumatic forms of SCI, including degenerative cervical myelopathy (DCM). Preclinical studies consistently demonstrate functional and histopathological improvements following riluzole administration. Phase I/II trials have provided evidence for its safety and tolerability in acute SCI patients, while the RISCIS and CSM-PROTECT trials, two landmark multicenter randomized controlled studies, along with their secondary analyses, revealed promising multidomain improvements in motor function, independence, and quality of life indices. Sub-studies have also established pharmacokinetic and pharmacodynamic frameworks for individualized dosing, and early biomarker analysis suggests potential for predictive stratification. SUMMARY: Riluzole represents a promising candidate for neuroprotection in traumatic and nontraumatic SCI. The consistency of favorable trends across multiple domains and strong support from preclinical studies highlight riluzole's value in orphan diseases such as SCI. Future directions should focus on refining the therapeutic window, optimizing PK/PD modeling, and identifying patient subgroups most likely to benefit. Its implementation in a multimodal treatment paradigm for acute SCI will be crucial for optimizing management protocols in this highly disabling condition.
Sound decisions: real-time ultrasound in the management of traumatic spinal cord injury.
Hofstetter CP, Sadeghi A, Ramkumar R … +2 more , Bruce M, Khaing ZZ
Curr Opin Neurol · 2025 Dec · PMID 41117137 · Publisher ↗
PURPOSE OF REVIEW: Traumatic spinal cord injury (tSCI) is a devastating neurological emergency with high morbidity and no proven therapies that reliably improve recovery. While early decompression and hemodynamic optimiz...
PURPOSE OF REVIEW: Traumatic spinal cord injury (tSCI) is a devastating neurological emergency with high morbidity and no proven therapies that reliably improve recovery. While early decompression and hemodynamic optimization are standard, clinicians lack imaging tools to stratify injury severity or monitor physiological responses in real time. Advances in high-resolution B-mode, contrast-enhanced ultrasound, and multiparametric approaches offer a unique opportunity to close this gap and improve patient-specific treatment strategies. RECENT FINDINGS: Ultrasound can: characterize injury morphology, revealing cord swelling, hemorrhage, and parenchymal disruption; verify and optimize cord decompression by visualizing restoration of the subarachnoid space, and cerebrospinal fluid pulsatility; assess cord perfusion in real time with contrast-enhanced ultrasound, and guide targeted interventions in acute and chronic tSCI, including therapeutic delivery, blood-spinal cord barrier modulation, and neuromodulation. Preclinical models and early clinical series increasingly validate these applications. SUMMARY: Integrating ultrasound into tSCI care could yield actionable biomarkers, enhance intraoperative and critical care decision-making, and accelerate the translation of novel therapies. Future priorities include standardizing imaging protocols, validating prognostic metrics, correlating imaging findings with long-term outcomes, and developing portable systems for continuous, patient-specific monitoring.
Overlapping mechanisms of epidural spinal cord stimulation for pain control and movement recovery.
Joiner EF, Bikson M, Carmel JB
Curr Opin Neurol · 2025 Dec · PMID 41076564 · Full text
PURPOSE OF REVIEW: Spinal cord stimulation (SCS) for pain control and movement recovery have developed under parallel conceptual frameworks. SCS for pain has traditionally targeted the dorsal columns, while SCS for movem...
PURPOSE OF REVIEW: Spinal cord stimulation (SCS) for pain control and movement recovery have developed under parallel conceptual frameworks. SCS for pain has traditionally targeted the dorsal columns, while SCS for movement recovery has targeted the large-diameter afferent fibers near the dorsal root entry zone. We review the evidence to support these parallel mechanistic frameworks and explore potential mechanistic overlap between the two fields. RECENT FINDINGS: Recent advances in closed-loop stimulation for pain and dorsal root (DR) stimulation for movement recovery speak to the value of these parallel mechanistic models in each field. However, review of the devices, electrode placement, and stimulation parameters used in both fields reveals overlap in the doses of SCS considered effective in each. Furthermore, evidence from finite element modeling suggests overlapping recruitment of dorsal column and dorsal root fibers from both midline and lateral stimulation. SUMMARY: There is evidence to support overlapping mechanisms of SCS for pain and movement recovery. The implications of potential mechanistic overlap warrant further investigation.
Emerging targeted therapies in meningiomas.
Yamazawa E, Sullivan E, Wakimoto H … +1 more , Brastianos PK
Curr Opin Neurol · 2025 Dec · PMID 41069194 · Publisher ↗
PURPOSE OF REVIEW: Patients with grade 2 and 3 meningioma have high recurrence rates and limited treatment options after failure of radiation and surgery. Recent advances in molecular profiling of these tumors have enabl...
PURPOSE OF REVIEW: Patients with grade 2 and 3 meningioma have high recurrence rates and limited treatment options after failure of radiation and surgery. Recent advances in molecular profiling of these tumors have enabled the investigation of novel targeted therapeutic approaches. RECENT FINDINGS: Innovative treatment strategies under investigation for recurrent high-grade meningiomas include targeted therapies, immunotherapy, and radionuclide-based approaches. Inhibition of angiogenesis, histone deacetylases, FAK, mTOR, and CDK4/6 pathways has shown early signs of activity in small clinical trials of patients with recurrent meningiomas. Immunotherapy, such as immune checkpoint inhibition (ICI), has also demonstrated prolonged disease control in a subset of patients. Larger randomized studies are needed for further investigation of the efficacy and safety of these newer therapies in patients with high-grade and recurrent meningioma. SUMMARY: Emerging molecularly driven treatment strategies show promise for the treatment of patients with high-grade meningiomas. Larger trials that incorporate molecular testing are warranted to fully evaluate their therapeutic potential.
Electrical and optogenetic spinal cord stimulation for movement recovery after spinal cord injury.
Henderson RP, Mondello SE, Moritz CT
Curr Opin Neurol · 2025 Dec · PMID 41069191 · Full text
PURPOSE OF REVIEW: In this review, we discuss electrical and optogenetic technologies for stimulating the spinal cord to improve movement after spinal cord injury (SCI). RECENT FINDINGS: Paralysis or paresis following SC...
PURPOSE OF REVIEW: In this review, we discuss electrical and optogenetic technologies for stimulating the spinal cord to improve movement after spinal cord injury (SCI). RECENT FINDINGS: Paralysis or paresis following SCI severely impairs control and movement of the extremities. Restoring movement in the upper and lower extremities is a top priority for this population. Invasive and noninvasive electrical stimulation of the spinal cord can modulate the activity of spinal circuits, resulting in improvements in motor and sensory function. More recently, optogenetic stimulation has emerged as another technique capable of modulating spinal circuity to facilitate movement recovery in animal models. Recent studies are offering new insights into the effects of parameter selection, multisite stimulation, and the combined effects of stimulation and wearable robotic exoskeletons, all with the goal of restoring movement after SCI. SUMMARY: Modulating the activity of the spinal cord via electrical and optogenetic stimulation is a promising intervention for improving movement after SCI. Future studies should determine optimal stimulation parameters, synergistic effects when combined with wearable robotics, and the safety of optogenetics in the human spinal cord. Such work will best position these emerging technologies for clinical translation.
Rare gliomas: standard treatment approaches and new target therapies.
Bruno F, Pellerino A, Pronello E … +1 more , Rudà R
Curr Opin Neurol · 2025 Dec · PMID 40990677 · Publisher ↗
PURPOSE OF REVIEW: Rare gliomas, including circumscribed astrocytic, glioneuronal, and neuronal central nervous system (CNS) tumours, though collectively uncommon, present significant clinical challenges due to their het...
PURPOSE OF REVIEW: Rare gliomas, including circumscribed astrocytic, glioneuronal, and neuronal central nervous system (CNS) tumours, though collectively uncommon, present significant clinical challenges due to their heterogeneity and limited therapeutic evidence. Conventional management has relied predominantly on surgery and radiotherapy. Advances in molecular profiling have revealed actionable targets, prompting a timely reassessment of treatment paradigms. This review aims to describe current standard treatments and recent advances in molecularly targeted approaches for rare gliomas. RECENT FINDINGS: Gross total surgical resection remains the primary therapeutic modality for rare gliomas, providing optimal tumour control and symptom relief. Radiotherapy offers additional benefit in case of subtotal resection or recurrent disease, particularly in WHO grade 3 tumours. In contrast, conventional chemotherapy has shown limited efficacy and is typically reserved for refractory or progressive cases.The discovery of actionable molecular alterations in a substantial subset of rare gliomas has led to increasing integration of targeted therapies into clinical management. Notable recent advances include the use of BRAF/MAPK pathway inhibitors (e.g., dabrafenib/trametinib, tovorafenib), NTRK inhibitors (e.g., larotrectinib, entrectinib), FGFR inhibitors (e.g., erdafitinib, pemigatinib), and mTOR inhibitors (e.g., everolimus), which have demonstrated meaningful clinical activity in select patient populations. SUMMARY: Precision oncology is rapidly transforming the treatment landscape for rare CNS tumours. Integration of targeted therapies into clinical protocols - ideally guided by multidisciplinary molecular tumour boards - is increasingly warranted. Future research must optimise timing, combination strategies, and overcome resistance, while new biomarkers and liquid biopsy tools are needed to guide the choice of therapy and monitor response in this underserved population.
Characterization, etiology, and management of neurocognitive impairment in patients with glioma: an evidentiary update.
Noll KR, Wefel JS
Curr Opin Neurol · 2025 Dec · PMID 40948080 · Publisher ↗
PURPOSE OF REVIEW: This review provides a summary of recent literature concerning neurocognitive functioning (NCF) in patients with glioma, including developments in assessment and characterization of NCF impairment, und...
PURPOSE OF REVIEW: This review provides a summary of recent literature concerning neurocognitive functioning (NCF) in patients with glioma, including developments in assessment and characterization of NCF impairment, understanding of etiologic contributors, and mitigation and intervention strategies. RECENT FINDINGS: NCF impairment remains ubiquitous in patients with glioma, despite recognition of the detrimental impact upon well being. Risk factors for NCF decline and the underlying neurophysiologic mechanisms continue to be unraveled, including individual genetic characteristics, dynamic tumor and treatment-related changes to local and whole-brain networks, inflammatory cascades, and influence of social determinants of health. Developments in glioma treatment may improve NCF outcomes, such as advances in brain mapping for safer resection and investigational approaches to radiation delivery, though evidence is largely preliminary. While traditional neuropsychological testing has demonstrated utility in this population, digital and other emerging assessment approaches require further study. Additionally, few strategies for management and rehabilitation of NCF impairment are well supported, though potentially efficacious intervention approaches are briefly highlighted. SUMMARY: Impairment of NCF arises from complex tumor and treatment-driven network injury. While development of management strategies has been relatively modest, future approaches may capitalize on the rapidly advancing understanding of etiological mechanisms underlying NCF impairment in patients with glioma.
Isocitrate dehydrogenase mutation and microenvironment in gliomas: do immunotherapy approaches matter?
Platten M
Curr Opin Neurol · 2025 Dec · PMID 40916936 · Publisher ↗
PURPOSE OF REVIEW: Gliomas with mutations in the gene for isocitrate dehydrogenase (IDH) display a unique immune microenvironment that is distinct from IDH-wildtype gliomas. This unique immune microenvironment is shaped...
PURPOSE OF REVIEW: Gliomas with mutations in the gene for isocitrate dehydrogenase (IDH) display a unique immune microenvironment that is distinct from IDH-wildtype gliomas. This unique immune microenvironment is shaped by 2-hydroxyglutarate (2-HG), an oncometabolite produced by mutant IDH. These features provide an opportunity to develop and test targeted immunotherapies for IDH-mutant gliomas. RECENT FINDINGS: IDH-mutant gliomas are characterized by an immunosuppressive tumor immune microenvironment (TIME) that suppresses the infiltration and activation of tumor-specific T cells. This is owed both to direct effects of the oncometabolite 2-hydroxyglutarate on glioma-infiltrating T cells and myeloid cells and indirect effects on the chemotactic profile of tumor cells. These immunosuppressive effects are reversed by IDH inhibitors recently approved for the treatments of IDH-mutant gliomas. At the same time, clinical trials have demonstrated encouraging results for targeted immunotherapies using vaccines targeting the most frequent mutation IDH1R132H. SUMMARY: The reversal of the immunosuppressive effects by IDH inhibitors has opened exciting avenues for combinatorial immunotherapies such as vaccines and immune checkpoint inhibitors.
Neurosyphilis in 2025: Erratum.
Curr Opin Neurol · 2025 Oct · PMID 40916892 · Publisher ↗
Abstract loading — click title to view on PubMed.
Progress in ALS research 2025.
Ludolph A
Curr Opin Neurol · 2025 Oct · PMID 40916891 · Publisher ↗
Abstract loading — click title to view on PubMed.
Agentic artificial intelligence in neuromuscular health: a new ecosystem for autonomous digital systems featuring multimodal integration, trial support, and real-world monitoring.
Schoser B
Curr Opin Neurol · 2025 Oct · PMID 40916890 · Publisher ↗
Abstract loading — click title to view on PubMed.
Autoimmune nodopathies: emerging insights and clinical implications.
Collet-Vidiella R, De Lorenzo A, Querol L
Curr Opin Neurol · 2025 Oct · PMID 40916889 · Publisher ↗
PURPOSE OF REVIEW: Autoimmune nodopathies (AN) are a recognized distinct group of immune-mediated peripheral neuropathies with unique immunopathological features and therapeutic implications. This review synthesizes rece...
PURPOSE OF REVIEW: Autoimmune nodopathies (AN) are a recognized distinct group of immune-mediated peripheral neuropathies with unique immunopathological features and therapeutic implications. This review synthesizes recent advances in their pathogenesis, diagnosis, and management, which have refined their clinical classification and informed targeted treatment strategies. RECENT FINDINGS: AN are characterized by autoantibodies targeting surface proteins in the nodal-paranodal area (anti-contactin-1, anti-contactin-associated protein 1, anti-neurofascin-155, anti-pan-neurofascin), predominantly of IgG4 subclass. Recent studies have delineated antibody subclass contributions to disease mechanisms and identified B-cell response patterns predictive of therapeutic outcomes. Despite clinical overlap with chronic inflammatory demyelinating polyradiculoneuropathy and Guillain-Barré syndrome, AN exhibit a distinct phenotype and a poor response to intravenous immunoglobulins. Multiple studies, including recent ones, report good response and long-term clinical remission with B-cell depleting therapies. Diagnostic assays such as cell-based assays and ELISA offer high accuracy, while biomarker-guided monitoring using antibody titers and serum neurofilament light chain supports individualized follow-up. SUMMARY: Emerging evidence consolidates AN as a nosologically and therapeutically distinct entity. Integration of immunopathological insights with biomarker-driven strategies enables precision diagnostics and targeted immunotherapy, improving clinical outcomes.
Heterogeneity of frequencies of motor neuron disease across ethnicities and geographical areas: focus on Arabic countries in the Mediterranean area.
Logroscino G, Giannoni-Luza S, Urso D … +1 more , Hamdi N
Curr Opin Neurol · 2025 Oct · PMID 40855953 · Full text
PURPOSE OF REVIEW: Although amyotrophic lateral sclerosis (ALS) epidemiology has been increasingly characterized in many regions, data from Arabic countries remain limited. This review aims to summarize the current knowl...
PURPOSE OF REVIEW: Although amyotrophic lateral sclerosis (ALS) epidemiology has been increasingly characterized in many regions, data from Arabic countries remain limited. This review aims to summarize the current knowledge on the burden of ALS in Arabic Mediterranean countries, with a particular focus on Egypt. RECENT FINDINGS: ALS exhibits significant geographic and ethnic variability in terms of incidence, phenotype, and genetic background. Data from the Global Burden of Disease Study 2021 show that Egypt has one of the lowest age-standardized rates of ALS incidence, prevalence, and mortality in the Mediterranean basin. During the past three decades, Egypt has seen a notable decline in ALS-related Disability-Adjusted Life Years and deaths, in contrast to neighboring countries. A national registry has recently been initiated to enhance epidemiological surveillance in the country. SUMMARY: ALS in Arabic Mediterranean countries presents a distinct epidemiological profile. These differences likely reflect a combination of genetic, demographic, and healthcare-related factors. Strengthening national registries and promoting regional collaborations will be crucial for gaining a deeper understanding of the determinants of ALS in these underrepresented populations.
Antisense oligonucleotide therapy in amyotrophic lateral sclerosis.
Erdi-Krausz G, Shaw PJ
Curr Opin Neurol · 2025 Oct · PMID 40832750 · Publisher ↗
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...
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.
Neurochemical biomarkers of amyotrophic lateral sclerosis: recent developments.
Verde F
Curr Opin Neurol · 2025 Oct · PMID 40832743 · Publisher ↗
REVIEW PURPOSE: To provide an overview of the recent developments in the field of neurochemical biomarkers of amyotrophic lateral sclerosis (ALS). RECENT FINDINGS: Neurofilaments, especially NFL, have been confirmed to b...
REVIEW PURPOSE: To provide an overview of the recent developments in the field of neurochemical biomarkers of amyotrophic lateral sclerosis (ALS). RECENT FINDINGS: Neurofilaments, especially NFL, have been confirmed to be good biomarkers for ALS. NFL may be diagnostically useful but its main role is as prognostic and pharmacodynamic biomarker. Inflammatory biomarkers, especially the chitinases, might also serve as pharmacodynamic biomarkers in treatment trials targeting neuroinflammation. GFAP could reflect cognitive-behavioural impairment. CSF dipeptides are diagnostic biomarkers for ALS caused by the C9ORF72 exanucleotide repeat expansion and may be used to confirm target engagement by experimental drugs. Levels of TDP-43 (virtually the ideal biomarker for ALS) in CSF and plasma have not been demonstrated to be consistently altered in ALS. However, promising advancements have been achieved in seed amplification assays for the protein, in its quantification in plasma extracellular vesicles, and in the measurement of CSF levels of a protein reflecting splicing dysfunction of TDP-43. Finally, blood phosphorylated tau has emerged as an ALS biomarker linked to lower motor neuron (or muscle) pathology. SUMMARY: NFL is still the best neurochemical biomarker for ALS. However, substantial advances have been recently made, especially regarding detection of TDP-43 and blood phosphorylated tau.
Sleep alterations in amyotrophic lateral sclerosis.
Lang C
Curr Opin Neurol · 2025 Oct · PMID 40832740 · Full text
PURPOSE OF REVIEW: This review summarizes recent evidence on sleep disturbances in amyotrophic lateral sclerosis (ALS), emphasizing their role as intrinsic features of the disease process rather than consequence of motor...
PURPOSE OF REVIEW: This review summarizes recent evidence on sleep disturbances in amyotrophic lateral sclerosis (ALS), emphasizing their role as intrinsic features of the disease process rather than consequence of motor decline. RECENT FINDINGS: Emerging data suggest that sleep disturbances such as sleep fragmentation, rapid eye movement sleep (REM) and non rapid eye movement sleep (NREM) alterations and circadian changes often precede classic motor symptoms. Structural and functional hypothalamic changes have been observed in early ALS, suggesting a direct role in sleep-wake dysregulation. In addition, impaired glymphatic clearance during sleep may contribute to neurodegeneration by impairing the removal of protein waste. Polysomnographic studies and cohort data support the presence of prodromal sleep abnormalities in both symptomatic patients and gene mutation carriers. Noninvasive ventilation has shown benefits not only in respiratory management but also in improving sleep quality and overall prognosis. SUMMARY: Sleep alterations in ALS are increasingly recognized as early indicators and potential modulators of disease progression. The hypothalamus and the glymphatic system emerge as key contributors to these disturbances, highlighting sleep as a therapeutic target. Understanding the role of sleep in ALS pathophysiology may aid in earlier diagnosis and novel intervention strategies aimed at modifying disease course.
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