PURPOSE OF REVIEW:Inclusion body myositis (IBM) is the most prevalent acquired myopathy in adults over 50 years of age, yet effective disease-modifying therapy has remained elusive. The longstanding debate over whether degeneration or inflammation is the primary driver has now given way to a model of bidirectional interplay. This review critically appraises advances published between January 2025 and June 2026, encompassing molecular pathomechanisms, early diagnostic strategies, disease-modifying therapies, and rehabilitation. RECENT FINDINGS:A pivotal mechanistic advance is the demonstration that TDP-43 nuclear depletion in IBM myonuclei generates cryptic exon-derived neoantigens that directly activate CD8 + T cells, molecularly unifying cell-autonomous degeneration and adaptive immune activation. In parallel, mitochondrial DNA leakage activates the cGAS-STING innate immune pathway prior to T cell infiltration. An endogenous compensatory mechanism involving the NORAD-Pumilio regulatory axis has also been identified. Clinically, preliminary data from the Phase 2/3 MUSCLE trial suggest a potential 50% slowing of progression in mild-to-moderate IBM with the anti-KLRG1 antibody ulviprubart, pending full peer-reviewed publication, while novel diagnostic and rehabilitation strategies further advance personalized care. SUMMARY:A molecular cascade from cell-autonomous TDP-43 dysfunction to cryptic epitope-driven immune activation could underlie the pathogenesis of IBM. Personalized multidisciplinary care integrating early diagnosis, targeted disease-modifying therapy, and advanced rehabilitation represents the emerging treatment paradigm.
PURPOSE OF REVIEW:Balance depends on accurate perception of self-motion and verticality and on multisensory integration for stance, and gait. In Parkinson's disease, balance is commonly impaired and variably affected by treatment. Although vestibular and multisensory contributions are increasingly recognized, progress is limited by fragmented evidence, inconsistent methods, and artifact-prone measures. We provide a consensus roadmap across four domains - video-oculography/vHIT, VEMPs, posturography, and perceptual paradigms - to improve clinical translation of balance research in Parkinson's disease. RECENT FINDINGS:An interdisciplinary taskforce conducted a comprehensive literature review and a modified Delphi process (≥80% agreement), using virtual meetings, surveys, and an in-person consensus session. Oculography/vHIT shows largely preserved aVOR in Parkinson's disease but is vulnerable to Parkinson's disease specific artifacts, requiring standardization. VEMPs relate to brainstem and non-motor features but are limited by EMG-dependent confounds. Posturography reveals impaired multisensory integration with visual dependence and cholinergic contributions; reactive-capacity measures outperform sway alone. Perceptual paradigms show task-specific distortions and increased variability linked to axial/postural syndromes. SUMMARY:This consensus offers a practical roadmap, de-emphasize aVOR/vHIT as primary unsteadiness outcomes; use VEMPs as ancillary measures; prioritize posturography probing adaptability and reactive stepping; integrate wearables and neurochemical imaging; and adopt consortium-level minimum datasets to enable reproducible, phenotype-aware advances in Parkinson's disease balance research.
PURPOSE OF REVIEW:We review recent electrophysiological advances that have refined our understanding of tic generation in Tourette syndrome by characterizing dysfunction across cortico-striato-pallido-thalamo-cortical (CSPTC) circuits and their time-resolved dynamics. We integrate evidence across spatial scales - from single-unit activity to large-scale network coupling - and examine how these findings provide a mechanistic framework for interpreting both invasive and noninvasive neuromodulation approaches. Finally, we discuss how electrophysiological signatures of tics and premonitory urges may serve as candidate biomarkers to guide future, dynamically informed interventions. RECENT FINDINGS:At the microscale, intraoperative recordings indicate that GPi neurons in Tourette syndrome exhibit a burst-pause firing pattern with phasic modulation preceding tic onset, consistent with transient pallidal disinhibition. At the mesoscale, LFP recordings from centromedian nucleus and aGPi show increased low-frequency (3-12 Hz) power and pallido-thalamic coherence during tics, accompanied by reduced phase synchrony, suggesting dysrhythmic rather than coordinated network activity. At the macroscale, combined intracranial and scalp EEG recordings demonstrate that thalamo-frontal alpha-band connectivity progressively declines in the ~1.3 s preceding tic onset, propagating from sensorimotor to prefrontal regions. Importantly, these pretic dynamics are captured by measures of inter-regional coupling rather than local power, highlighting the relevance of distributed network interactions. These findings are beginning to inform neuromodulation strategies across modalities. Deep brain stimulation (DBS) targeting thalamic or pallidal regions provides clinically meaningful tic reduction, while connectomic analyses emphasize the role of distributed fibre pathways over single anatomical targets. In parallel, noninvasive approaches show mixed results: cortical stimulation techniques such as rTMS and tDCS have yielded inconsistent effects, whereas peripheral rhythmic stimulation, such as 10 Hz median nerve stimulation, has demonstrated efficacy in controlled trials, potentially through modulation of sensorimotor network dynamics. SUMMARY:Electrophysiological evidence across spatial scales supports a model of Tourette syndrome as a disorder of dynamic CSPTC circuit dysfunction. At the cellular level, GPi neurons exhibit a sparse but high-intensity bursting regime, with activity changes preceding tic onset. At the population level, low-frequency oscillations in pallido-thalamic networks track tic severity and distinguish tics from voluntary movements. At the network level, thalamo-frontal alpha-band coupling appears to exert a stabilizing influence, whose progressive reduction precedes tic expression. Together, these findings suggest that tic generation arises from temporally evolving disruptions in distributed network coordination rather than from static abnormalities within isolated regions. This framework provides a common basis for understanding both invasive and noninvasive neuromodulation and supports the development of electrophysiological biomarkers for adaptive, closed-loop therapeutic strategies.
PURPOSE:Studies of eye movements have evolved from clinical phenomenology to a probe of neural circuitry, cognition, and behavior offering a powerful, noninvasive window into nervous system function. In Parkinson's disease (PD), ocular motor control has emerged as a uniquely informative model system, reflecting dysfunction across motor, cognitive, and executive domains. RECENT FINDINGS:Recent advances span four interconnected areas: executive behavior and cognition, gait and freezing of gait (FOG), neuromodulation, and machine learning. Antisaccades and related paradigms reveal early and progressive executive dysfunction in PD, linked to dopaminergic disruption of fronto-striatal and basal ganglia circuits. Naturalistic eye-tracking metrics further act as proxy markers of cognition, planning, and emotion processing. Oculomotor abnormalities also have direct functional consequences for visual search, walking, turning, and FOG, with shared neural substrates in frontal cortex, basal ganglia, and mesencephalic locomotor networks. Deep brain stimulation provides causal insight into these circuits, demonstrating target-, parameter-, and task-specific trade-offs between motor facilitation and inhibitory control. Finally, machine learning and emerging virtual reality (VR)- and mobile-based eye-tracking technologies enable high-dimensional analysis, early diagnosis, cognitive staging, and prognostic prediction, including identification of prodromal FOG. SUMMARY:Collectively the research has offered scalable biomarkers and mechanistic insight that bridge cognition, movement, and neuromodulation.
PURPOSE OF REVIEW:This review summarizes recent advances in the clinical classification, diagnostic approaches, genetic spectrum and therapeutic strategies for dystonia. RECENT FINDINGS:Dystonia is a heterogeneous movement disorder that may present as an isolated motor syndrome or as part of a broader neurological condition. Early recognition of its clinical features is essential for accurate diagnosis and timely treatment. Recent advances in genetics have identified multiple causative genes and provided insights into the molecular basis of dystonia; however, mechanism-based therapies remain limited. We highlight updated clinical classification systems and diagnostic algorithms, along with key clinical features that may indicate specific genetic forms of dystonia. Emerging insights into neuronal and circuit-level dysfunction are discussed, emphasizing underlying molecular mechanisms. In addition, we review current treatment strategies, including pharmacological therapies, botulinum toxin injections, and neuromodulation approaches such as deep brain stimulation. SUMMARY:Integrating clinical phenotyping with genetic and mechanistic insights provides a more precise diagnostic framework for dystonia. This approach facilitates improved patient stratification and lays the foundation for the development of mechanism-targeted therapies, ultimately advancing precision medicine in dystonia.
PURPOSE OF REVIEW:Functional movement disorders (FMD) are common and potentially reversible causes of movement disorders, yet they remain under-recognized and frequently misdiagnosed. RECENT FINDINGS:Diagnosis has shifted from an exclusion-based model to a positive rule-in approach grounded in positive clinical signs such as inconsistency (distractibility and variability), with electrophysiology providing useful support in selected cases. Current pathophysiological models suggest that FMD arise from interacting abnormalities in predictive coding, sensorimotor integration, altered sense of agency, maladaptive attentional focus, and disrupted limbic-motor network connectivity. These mechanisms may contribute both to symptom generation and maintenance. Prognosis is variable and often guarded, highlighting the importance of early diagnosis and timely intervention. Management should rely on a clear and validating explanation of the diagnosis, individualized rehabilitation focused on movement retraining, and tailored psychotherapy addressing perpetuating cognitive, behavioral, and emotional factors. Pharmacological treatment has a mainly an adjunctive role, particularly for comorbid psychiatric symptoms, pain, and sleep disturbances. SUMMARY:FMD require an integrated, multidisciplinary, and patient-centered approach to optimize functional recovery and long-term outcomes.
PURPOSE OF REVIEW:Autoimmune myelitis represents a heterogeneous group of disorders whose classification has evolved substantially over the past decade. Advances in antibody diagnostics and the widespread use of immune checkpoint inhibitors (ICIs) in oncology have reshaped current concepts, revealing mechanistic and clinical overlaps between antibody-mediated, paraneoplastic, and treatment-induced myelopathies. RECENT FINDINGS:Antibody-associated myelitis, including myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), aquaporin-4 (AQP4)-immunoglobulin G (IgG)-positive NMOSD and glial fibrillary acidic protein (GFAP) astrocytopathies, accounts for many cases previously labeled idiopathic. Paraneoplastic myelitis is rare but severe, possibly overlapping with NMOSD or GFAP astrocytopathies. In parallel, ICIs have emerged as a novel trigger of immune-mediated myelitis, capable of inducing de novo inflammatory spinal cord syndromes or unmasking latent autoimmune diseases, including AQP4-IgG-positive NMOSD and GFAP astrocytopathies but not MOGAD. SUMMARY:Autoimmune myelitis is best conceptualized within an etiological and context-dependent framework integrating antibody status, oncological evaluation, and exposure to immunotherapies. The expanding interface between astrocytopathies, paraneoplastic syndromes, and ICI-associated myelitis has important diagnostic and therapeutic implications, underscoring the need for systematic antibody testing and cancer screening in patients with inflammatory myelopathy.
PURPOSE OF REVIEW:Autoimmune encephalitis (AE), paraneoplastic neurological syndromes (PNS), and glial antibody-mediated disorders (for example, AQP4-NMOSD) are traditionally classified based on the target antigens of their respective autoantibodies. However, recent insights from immunogenomics, single-cell sequencing, and neuropathology indicate that T cell programs substantially influence disease initiation, localization, and chronicity. This review highlights three emerging dimensions of T-cell involvement - circulating exhausted-like helper T-cell memory, intrathecal T-B cooperation, and parenchymal tissue-resident cytotoxicity - that offer new perspectives on clinical and pathological features across these disorders. RECENT FINDINGS:In AQP4-NMOSD, circulating exhausted-like CD4 + T cells may constitute a durable autoreactive memory reservoir capable of re-initiating plasmablast responses. In LGI1- and CASPR2-associated encephalitis, systemic and intrathecal CD4 + differentiation appears to support systemic antibody maturation and local plasmablast expansion, with emerging hints of some accompanying CD8 + -mediated tissue injury. In contrast, in PNS and intracellular antigen-associated AE, CD8 + T cell-mediated cytotoxicity dominates and is characterized by parenchymal CD8 + tissue-resident memory (TRM) signatures. SUMMARY:These T-cell dimensions may provide a useful framework for understanding clinical paradoxes - such as relapse despite B-cell depletion, persistent memory dysfunction in IgG4-AE, and therapeutic inefficacy in PNS - and suggest opportunities for therapeutic strategies targeting exhausted T-cell memory, intrathecal cooperation, or TRM stability.
Purpose of review This review describes the mechanisms of paraneoplastic neurological syndromes (PNS) and the recent advances underlying these. Recent findings This review covers advances in the understanding of the immunobiology of PNS. Specifically, evidence that PNS associated with antibodies against intracellular antigens are T-cell mediated processes, of interferon-γ signaling, major histocompatibility complex (MHC) class I upregulation, and granzyme mediated neuronal death. In contrast, PNS with antibodies against neuronal surface antigens are antibody-mediated and cause reversible neuronal dysfunction. Further, the perennial question of why only few patients develop these disorders is emerging from studies of tumor genomics and host HLA associations. Finally, immune checkpoint inhibitors have demonstrated the role of immune tolerance breakdown in the development of these disorders. Summary These advancements in understanding of mechanisms of PNS have several implications for clinical practice and research. For clinical practice, these findings may lead to prognostication of risk of PNS in cancer patients and potential novel therapeutic approaches. For research, these findings have important implications for understanding tumor immunology, and immune tolerance.
PURPOSE OF REVIEW:Cognitive dysfunction in multiple sclerosis (MS) has gained increasing attention over recent decades, reflecting its substantial effects on day-to-day functioning and the limited availability of targeted therapies. This review addresses contemporary advances in the role of cognition to detect disease progression, examines biological and MRI correlates of cognitive dysfunction, and summarizes the evidence for treatment effects. RECENT FINDINGS:Cognitive changes can capture both acute relapse-related drops (including isolated cognitive relapses) and gradual decline consistent with progression independent of relapse activity (PIRA). Among fluid markers, serum neurofilament light chains relates to cognition mostly in relapsing disease, whereas glial fibrillary acidic protein seems to track global progression more than cognitive changes. Cerebrospinal fluid (CSF) candidate markers (CHI3L1, parvalbumin) and synaptic proteins (SNAP-25, neurogranin, β-synuclein) may help identifying patients at higher risk of cognitive decline. MRI demonstrates that grey-matter pathology best explains long-term cognitive trajectories while newer readouts (radiomics, quantitative susceptibility mapping of deep-grey nuclei, structural-functional disconnection and multiplex network indices, and choroid-plexus/glymphatic measures) add mechanistic and prognostic specificity beyond lesion burden and bulk atrophy. Data-driven cognitive phenotyping yields reproducible, biologically anchored profiles that outperform dichotomous impaired/preserved labels. Therapeutically, higher-efficacy disease-modifying therapies show the clearest association with preserved processing speed; cognitive rehabilitation, augmented in some settings by transcranial direct-current stimulation, produces additional gains. SUMMARY:Routine assessment and monitoring of cognitive functions should be embedded in MS care to detect relapse-related changes and progressive decline. Identifying fluid and MRI biomarkers of cognitive dysfunction may help individuate novel targets and specific treatments.
Purpose of reviewIt is increasingly recognized that reactive oxygen and nitrogen species (ROS and RNS) are not only damaging molecules, but also essential signaling molecules regulating functions on organellar, cellular, organ, and organism levels. Nevertheless, damaging capacity of different ROS and RNS are connected to almost all diseases, including (neuro-)inflammation. One of the most frequent neuroinflammatory diseases is multiple sclerosis (MS). In this opinion article, we discuss recent advances in knowledge about oxidative and nitrosative damage, redox regulation, and the related ferroptotic cell death mechanism in initiation and progression of MS.Recent findingsSpecific improvement of supportive or inhibition of harmful redox processes in either brain or immune cells showed great impact on disease severity in MS models. Moreover, (circulating) markers of oxidative damage may hold promise as a supplementary diagnostic tool to differentiate different subtypes of MS.SummaryOxidative damage is well established as driver of MS. Nevertheless, molecular redox mechanisms underlying initiation and progression of MS are not well known. This existing research gaps impedes the establishment of successful antioxidative therapies.
PURPOSE OF REVIEW:The prodromal phase of migraine is highly prevalent and can be very disabling. In this review, we seek to understand the clinical features of prodrome and its underlying pathophysiology. Our aim is to assess the impact of early treatment of migraine during the prodromal phase. RECENT FINDINGS:A recent phase 3 trial showed ubrogepant is effective at preventing migraine during the prodromal phase. Further studies have shown it is effective in reducing disabling symptoms of the prodrome itself and positive patient reported outcomes. SUMMARY:The prodromal phase of migraine presents the earliest opportunity to treat migraine and prevent disability. Studies have shown that the use of medications during this phase of migraine to be effective with recent studies showing ubrogepant is effective when used during prodrome.
PURPOSE OF REVIEW:First- and second-line medical and surgical therapies for trigeminal neuralgia (TN) may have limited efficacy or tolerability in some individuals. In addition, even when these therapies are initially successful, efficacy frequently wanes over time. This narrative review presents medication options for intractable trigeminal neuralgia with a focus on new and upcoming therapies. RECENT FINDINGS:Lacosamide, eslicarbazepine, and botulinum toxin are increasingly used for intractable TN, with recent studies demonstrating efficacy. Basimglurant and vixotrigine (BIIB074) are investigational agents currently or recently studied for treatment of TN. Intravenous (i.v.) sodium channel blockers, i.v. magnesium, multiple formulations of lidocaine, and sumatriptan can be used for acute treatment of intractable TN. SUMMARY:Multiple medical therapies exist for treatment of intractable TN, with newer options demonstrating efficacy in recent studies. Investigational agents are currently being studied as potential future options for management of intractable TN.
Purpose of review:This review evaluates recent advances in the development of translocator protein (TSPO) - and purinergic receptor-binding PET tracers and highlights the capacity of TSPO-PET-imaging to capture microglial activation across multiple regions of interest in multiple sclerosis brain. We discuss the added value of integrating PET-derived measures with fluid and metabolic biomarkers, as well as their successful application in recent clinical trials.Recent findings:Recent research highlights PET as a robust molecular imaging tool for detecting microglial activation and implicates dysregulated microglial activity as a key driver of smouldering multiple sclerosis pathology. PET-detectable microglial activation appears not merely as a secondary response to neuroaxonal injury but is increasingly recognized as an integral inflammatory component of ongoing pathological processes that lead to future brain atrophy and clinical deterioration.Summary:Recent advances establish PET as an essential research tool for evaluating the presence of smouldering inflammation in MS brain not detectable using MRI. Furthermore, PET-based methods have proven suitable for measuring glial responses to potentially neuroprotective therapies currently under development.
Purpose of the reviewThe evaluation of treatment response in multiple sclerosis (MS) has become increasingly nuanced as the field shifts from a primarily relapse-oriented perspective toward a more comprehensive understanding of the continuous interaction between inflammatory and neurodegenerative mechanisms.Recent findingsTraditional clinical measures, while indispensable, capture only a fraction of the disease process and are insufficient to detect the insidious progression that accounts for a substantial proportion of long-term disability. Enhanced functional assessments provide greater sensitivity to subtle clinical deterioration, and MRI remains the principal modality for identifying subclinical focal inflammatory activity. In parallel, biomarkers of neurodegeneration, including inner retinal layer thinning measured by optical coherence tomography (OCT) and fluid biomarkers such as serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP), offer complementary insights into diffuse pathological processes that elude conventional monitoring.SummaryA personalized monitoring strategy that integrates clinical assessment, imaging and fluid biomarkers holds the greatest promise for improving the detection of subclinical disease activity, refining risk stratification, and enabling more informed and individualized treatment decisions in contemporary MS care.
Purpose of reviewBrain MRI is central to the diagnostic work-up of autoimmune encephalitis (AE). This review summarizes established patterns on routine MRI sequences across antibody-defined AE types and highlights emerging quantitative and network-based approaches aimed at improving sensitivity, phenotypic stratification, and prognostication.Recent findingsConventional MRI reveals syndrome-associated patterns that can support diagnosis in several AE types, including medial temporal involvement in LGI1, CASPR2, and GABA(B) receptor encephalitis; multifocal cortico-subcortical lesions in GABA(A) receptor encephalitis, and radial perivascular enhancement in GFAP astrocytopathy. Longitudinal studies show that regional and global atrophy better reflect cumulative injury and clinical outcome than acute lesions in entities such as NMDA receptor encephalitis or IgLON5 antibody-mediated disease. Basic quantitative measures derived from routine sequences can detect microstructural abnormalities in normal-appearing tissue. Advanced techniques including quantitative MRI, diffusion tensor imaging, and resting-state functional MRI demonstrate widespread structural and functional network disruption beyond visible lesions. Translational animal studies further link imaging changes to antibody-mediated synaptic dysfunction.SummaryConventional MRI remains indispensable for differential diagnosis and pattern recognition in AE. Pragmatic approaches such as volumetry and basic quantitative metrics are closest to clinical implementation, whereas advanced techniques require further standardization and validation. Together, these developments position MRI to evolve from a primarily diagnostic tool toward precision phenotyping, prognosis, and longitudinal monitoring in AE.
Purpose of reviewMultiple sclerosis is a clinically heterogeneous disease that is driven by complex immune mechanisms. This review summarizes recent methodological advances in immunophenotyping and discusses clinical implications for diagnosis, prognosis, therapy selection, and monitoring.Recent findingsMethodological advances like high-dimensional flow cytometry and single-cell technologies aim to define Multiple sclerosis immunological endophenotypes associated with different disease trajectories. Novel spectral flow and mass cytometry panels reveal distinct immune cell subsets. Myeloid cell populations have been identified in aggressive disease variants and tissue-resident T cells in cerebrospinal fluid. Clinically, baseline immune signatures aim to predict disease progression and treatment response. Patients with a highly inflammatory immune profile have been found to exhibit more rapid progression and to be prone to treatment failure. Immunophenotyping may therefore guide treatment, from identifying those at risk of Alemtuzumab-induced autoimmunity to monitoring B-cell repopulation for personalized dosing schedules.SummaryImmunophenotyping enables increasingly precise characterization of Multiple sclerosis immuno-pathogenesis. While not yet routine, these tools show promise for improving differential diagnosis, individualizing therapy initiation and monitoring. Ongoing research and standardization are paving the way towards precision immunology-approaches in clinical practice.
