Current Opinion In Neurology[JOURNAL]
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200 papers
Barriers to providing movement disorders care in India.
Shah H, Kukkle PL
Curr Opin Neurol · 2025 Aug · PMID 40377651 · Publisher ↗
PURPOSE OF REVIEW: Movement disorders (MD) represent a growing healthcare challenge in India, where a diverse population and limited resources complicate diagnosis and management. This review aims to identify and categor...
PURPOSE OF REVIEW: Movement disorders (MD) represent a growing healthcare challenge in India, where a diverse population and limited resources complicate diagnosis and management. This review aims to identify and categorize the systemic, socio-economic, cultural, educational, and infrastructural barriers impeding timely and effective MD care, drawing on literature spanning rural and urban contexts. RECENT FINDINGS: Recent studies show low awareness of MD treatments - such as deep brain stimulation and botulinum toxin therapy - among both patients and clinicians. Socio-economic disparities, particularly in rural areas, combine with limited specialist availability and fragmented referral systems exacerbate care gaps. Meanwhile, gender biases, stigma, and reliance on alternative medicine further delay appropriate interventions. India's partial insurance coverage and insufficient policy frameworks constrain long-term management, although select government initiatives and community-level strategies offer promise. Technological approaches, including telemedicine, show potential for expanding care access. SUMMARY OF FINDINGS: Multiple interwoven factors hinder optimal MD care in India, diminishing patient outcomes and quality of life. Targeted educational campaigns, enhanced specialist training, improved insurance coverage, and robust policy guidance are crucial. By addressing these issues in a coordinated manner, India can significantly improve the delivery and effectiveness of MD care across its diverse regions.
Immunology of multiple sclerosis: an update.
Kirschner P, Pawlitzki M, Hartung HP … +1 more , Meuth SG
Curr Opin Neurol · 2025 Jun · PMID 40326581 · Publisher ↗
PURPOSE OF REVIEW: The immunological processes that lead to multiple sclerosis (MS) and occur during the progressive phase of the disease are manifold and still not well understood. This review summarizes new insights on...
PURPOSE OF REVIEW: The immunological processes that lead to multiple sclerosis (MS) and occur during the progressive phase of the disease are manifold and still not well understood. This review summarizes new insights on this topic that were gained through recent studies with diverse scientific approaches. RECENT FINDINGS: While genetic risk clearly contributes to MS, external factors play a key role in its pathogenesis as well. Epstein-Barr virus infection correlates significantly with MS risk and seems to be a major causal factor. Even though our knowledge on the human gut microbiome and its connection to the central nervous system is far from being complete, several studies have proven that the gut-brain axis influences neuroinflammation and disease progression in MS. It has become much clearer that MS is not solely a T cell-mediated disease but is also strongly driven by B cells and pathogenic antibodies. Beyond the peripheral immune cells, glial cells and their interactions with neurons are important players contributing to disease activity and progression in MS. SUMMARY: Taken together, recent publications on immunological processes in the context of MS implicate a multitude of noncanonical mechanisms that need to be further explored regarding their interplay and contribution to the degenerative course of the disease.
Migraine in women: a review.
Ghadiri-Sani M
Curr Opin Neurol · 2025 Jun · PMID 40265504 · Publisher ↗
PURPOSE OF REVIEW: The purpose of this review is to provide an update on the clinical course and management of migraine in women. RECENT FINDINGS: Migraine is two to three times more prevalent in women who report a longe...
PURPOSE OF REVIEW: The purpose of this review is to provide an update on the clinical course and management of migraine in women. RECENT FINDINGS: Migraine is two to three times more prevalent in women who report a longer, more severe attacks with more disability, an increased risk of recurrence, and a longer recovery period. Consequently, women use more acute and preventive medications, have more comorbid conditions and are more likely to run a chronic disease course.Real-life experience and evidence suggest that onabotulinumtoxinA and the newer generation antibody treatments against the calcitonin gene-related peptide (CGRP) ligand and its receptor are highly effective in the management of migraine in women.Pregnancy, breast feeding, and menstrual cycles should be taken into account when treating women with migraine. Topiramate and sodium valproate should be avoided in women of childbearing age (WCBA). Hormonal options can be considered in menstrual or menopausal migraines. NSAIDs and prostaglandins such as mefenamic acid can be used at onset of menstrual migraine. Venlafaxine can be effective in menopausal migraine while also treating the vasomotor symptoms. Migraine usually improves during pregnancy; however, if required nonpharmacological options should be considered. SUMMARY: Effectively managing migraine in women of productive and reproductive age, can reduce the socioeconomic burden of this debilitating disease.
Burning vertex syndrome: a novel unclassified headache - its preliminary observations, and possible mechanisms.
Thomas P, Yambao PEL
Curr Opin Neurol · 2025 Jun · PMID 40208092 · Publisher ↗
PURPOSE: Not all headaches are fully defined or characterized by the current classification systems. The variability in headache descriptions and presentation may be influenced by individual or group factors, or may even...
PURPOSE: Not all headaches are fully defined or characterized by the current classification systems. The variability in headache descriptions and presentation may be influenced by individual or group factors, or may even suggest the discovery of a new or an atypical phenotype. This paper aims to describe a novel headache syndrome characterized by a burning sensation on the vertex. RECENT FINDINGS: Demographic and clinical profiles of 25 patients from a referral headache center in India were analyzed. The syndrome presents as episodic, burning headaches on the vertex (10-20 cm diameter). Most patients were women (16/25), with a mean age of 40.96 years (SD+ 0.75). Episodes occurred 1-3 times weekly or daily, lasting <4 h (range: 1 min to 24 h). Associated symptoms included nausea, vomiting, photophobia, phonophobia, or autonomic features (76%). Common comorbidities were hypertension, diabetes, and polycystic ovarian disease. Neurological exams were normal, except for a slight local temperature rise in 2 patients. Treatment responses varied, though two patients reported reduced frequency and severity after greater occipital nerve (GON) block. SUMMARY: This syndrome is not completely compatible with any other primary headache disorders like nummular headache, migraine, cluster, or tension-type headaches. It potentially involves small fiber pathways from the scalp. Further studies are needed to better understand its clinical features, gender predilection, mechanisms, biomarkers, and treatment options.
Re-defining progression in multiple sclerosis.
Lambe J, Ontaneda D
Curr Opin Neurol · 2025 Jun · PMID 40197617 · Publisher ↗
PURPOSE OF REVIEW: The purpose of this article is to provide an overview of progression in multiple sclerosis (MS), including definitions, pathological mechanisms, and evidence that progressive biology begins early in th...
PURPOSE OF REVIEW: The purpose of this article is to provide an overview of progression in multiple sclerosis (MS), including definitions, pathological mechanisms, and evidence that progressive biology begins early in the disease course. RECENT FINDINGS: Definitions of MS clinical course have been refined to acknowledge the presence of both relapse and progression biology throughout the disease. Progression independent of relapse activity represents a significant proportion of disability worsening in relapsing-remitting MS (RRMS) disease. Progression in MS appears to be caused by the complex interplay of multiple processes, including nonresolving inflammation, microglial activation, oxidative stress, mitochondrial dysfunction, energetic failure, and neuro-axonal degeneration. These processes appear to begin in the earliest disease stages and their contribution to clinical phenotypes is dynamic over time. Promising results from clinical trials of tolebrutinib, in particular, underline the utility of targeting both innate and adaptive immune mechanisms to reduce disability accumulation. SUMMARY: Pathological processes that underpin MS progression are detectable early in RRMS, evolve throughout the disease course and correlate with disability accumulation. Progression in MS should not be defined dichotomously - the focus instead should be on recognizing progressive components based on clinical measures and biomarkers early in the disease to better individualize treatment strategies.
Recent developments in multiple sclerosis neuropathology.
Stadelmann C, Franz J, Nessler S
Curr Opin Neurol · 2025 Jun · PMID 40178490 · Full text
PURPOSE OF REVIEW: Neuropathological studies in human brain tissue are indispensable for our understanding of disease mechanisms in multiple sclerosis (MS). They inform concepts of lesion evolution, tissue regeneration a...
PURPOSE OF REVIEW: Neuropathological studies in human brain tissue are indispensable for our understanding of disease mechanisms in multiple sclerosis (MS). They inform concepts of lesion evolution, tissue regeneration and disease progression, and ideally reveal new disease mechanisms and therapeutic targets. Here we review recent neuropathological studies that have advanced our knowledge of MS pathogenesis. RECENT FINDINGS: Recent cohort studies support the notion that different clinical MS disease phenotypes share underlying pathological features, and that clinical and pathological heterogeneity is derived from a variable combination of innate and adaptive inflammation, demyelinating activity, and neuroaxonal loss. Importantly, emerging technologies for spatial transcriptome analysis enable an unprecedented glimpse into the cellular composition and molecular mechanisms involved in lesion evolution. These promising technologies will help identify the identification of molecular hubs governing tissue damage and regeneration. SUMMARY: Recent neuropathological studies helped to identify tissue correlates of disability and disease progression. Substantial progress in molecular brain tissue analysis revealed the complexity of MS-related tissue features. Close collaboration between tissue-based, molecular, bioinformatic, pharmacologic, imaging and clinical experts is needed to continue to advance the field, particularly for the benefit of people with progressive MS.
Cannabinoids in headache: helpful or harmful?
Kuruvilla DE
Curr Opin Neurol · 2025 Jun · PMID 40152937 · Publisher ↗
PURPOSE OF REVIEW: Cannabinoids have gained attention as a potential treatment for headache disorders, including migraine and cluster headache. While some studies suggest cannabinoids may provide analgesic and anti-infla...
PURPOSE OF REVIEW: Cannabinoids have gained attention as a potential treatment for headache disorders, including migraine and cluster headache. While some studies suggest cannabinoids may provide analgesic and anti-inflammatory effects, concerns remain regarding their potential for overuse headache, cognitive impairment, and psychological dependence. This study critically evaluates the current evidence on cannabinoids in headache treatment, weighing their benefits and risks. RECENT FINDINGS: With the migraine treatment landscape expanding faster than ever, recent studies explore immune cells as a target for cannabinoids. Immune cells express cannabinoid and CGRP (calcitonin gene-related peptide) receptors. As a result, cannabinoids might potentially modulate the efficacy of current CGRP-targeting drugs. Additionally, emerging studies suggest that cannabinoids may enhance neuronal resilience and mitigate central sensitization in chronic migraine. Research into optimal delivery mechanisms, including inhaled, sublingual, and transdermal formulations, is also expanding. SUMMARY: Cannabinoids are being studied as a potential treatment for headache disorders, particularly migraine, due to their interaction with the endocannabinoid system, which regulates pain, inflammation, and vascular function. Studies suggest cannabinoids may help reduce headache frequency, alleviate pain, and improve sleep, though concerns remain about dependency, cognitive impairment, and medication overuse headache. While retrospective studies indicate benefits, the lack of standardized dosing, long-term safety data, and controlled trials limits conclusive recommendations. Comparisons with conventional treatments show mixed results, with cannabinoids presenting variable effectiveness and a risk of adverse effects. Further research, including randomized controlled trials, is needed to establish optimal dosing, safety, and efficacy in headache management.
Monitoring multiple sclerosis: digital and fluid phase biomarkers.
Ward K, Reddel S, Leocani L … +1 more , Barnett M
Curr Opin Neurol · 2025 Jun · PMID 40152030 · Publisher ↗
PURPOSE OF REVIEW: Monitoring of disease activity and treatment response in multiple sclerosis (MS) currently relies on the integration of qualitative clinical and radiological data that is of limited predictive value. A...
PURPOSE OF REVIEW: Monitoring of disease activity and treatment response in multiple sclerosis (MS) currently relies on the integration of qualitative clinical and radiological data that is of limited predictive value. An array of quantitative digital and fluid biomarkers, many on the cusp of broad clinical translation, is expected to herald a new era of data-driven therapeutic strategy, particularly with respect to the sequencing of disease-modifying therapies (DMTs). Available highly-effective DMTs, which largely abolish acute inflammatory activity in early, relapsing MS, have a limited impact on progressive MS disease biology. However, robust digital and fluid biomarkers of progression independent of relapse activity (PIRA) have emerged as a major unmet need, fuelled by the imminent availability of treatments that target pathomechanisms such as chronic active or smouldering brain inflammation. RECENT FINDINGS: The criteria for MS diagnosis incorporate both imaging and cerebrospinal fluid (CSF) biomarkers of the disease, which lacks a single diagnostic 'test'. The recent validation of objective and quantitative CSF biomarkers, such as the k-FLC index, promises to improve diagnostic accuracy, particularly in patients with atypical or minor imaging changes. Precision monitoring of disease and is response to therapy is being transformed by the advent of clinically integrated, quantitative digital imaging tools; digital wearables and patient reported outcomes, including cognitive batteries delivered on personal devices; and an array of ultra-sensitive, readily-obtained serum fluid biomarkers that indicate the severity of tissue injury in MS. The promise of data-driven therapeutic strategy is being further explored in multimodal digital/fluid and digital twin biomarker studies that incorporate predictive artificial intelligence algorithms. SUMMARY: Here, we review the key near-term biomarkers that will guide individualised therapy for people with MS, targeting no evidence of disease activity (NEDA) in both early relapsing and established disease. In the medium term, composite digital and fluid biomarkers, integrated with clinical outcomes and underpinned by predictive artificial intelligence will have a transformative effect on the management of MS.
Multiple sclerosis: advances and challenges in diagnosis.
Tenembaum S, Hartung HP
Curr Opin Neurol · 2025 Jun · PMID 40145196 · Publisher ↗
PURPOSE OF REVIEW: This article explores the most recent developments in multiple sclerosis (MS), including a selection of advances in diagnostic neuroimaging markers. The proposed revision of diagnostic criteria, new co...
PURPOSE OF REVIEW: This article explores the most recent developments in multiple sclerosis (MS), including a selection of advances in diagnostic neuroimaging markers. The proposed revision of diagnostic criteria, new concepts on the prodromal period, and differential diagnosis of MS are included as well. RECENT FINDINGS: Interesting changes have been introduced to the recently proposed 2024 revisions of MS diagnostic criteria. Optic nerve is proposed as the 5 th CNS topography, additional advanced MRI markers are included, as well as specific cases of "radiologically isolated syndrome" considered at risk of future relapses.The diagnostic power of the central vein sign, paramagnetic rim lesion, and cortical lesions have been demonstrated in recent lines of research in adult and pediatric patients with MS. The contribution of cortical lesions, slowly expanding lesions, choroid plexus enlargement, paramagnetic rim lesions, leptomeningeal enhancement, in addition to measurement of brain and spinal cord atrophy, have expanded our understanding of early disease progression. SUMMARY: This review highlights a selection of recent studies that have significantly contributed to increase the accuracy of MS diagnosis in both pediatric and adult patients, and demonstrated the potential to improve the early detection of disease progression.
Red flags in multiple sclerosis.
Bulus E, Altintas A, Siva A
Curr Opin Neurol · 2025 Jun · PMID 40145176 · Publisher ↗
PURPOSE OF REVIEW: The diagnosis of multiple sclerosis (MS) is often challenging and misdiagnosis remains an important contemporary problem, with considerable consequences for patients. This review aims to specify the ap...
PURPOSE OF REVIEW: The diagnosis of multiple sclerosis (MS) is often challenging and misdiagnosis remains an important contemporary problem, with considerable consequences for patients. This review aims to specify the appropriate approach in differential diagnosis of MS, highlight the clinical and paraclinical red flags and create a new perspective to the clinicians. RECENT FINDINGS: The accurate diagnosis of MS is challenged by a broad and heterogeneous spectrum of diseases. The differential diagnosis should be based on the combined evaluation of typical clinical, radiological and laboratory findings. Studies have been recently published reported that 7.1-24.4% of patients have been misdiagnosed with MS. The most frequent correct alternative diagnoses were white matter ischemic disease and migraine. SUMMARY: Differential diagnosis of MS requires a holistic approach dependent on the clinical presentation and accompanied by vigilance for clinical and paraclinical red flags suggesting alternative diagnoses. Misdiagnosis could have the potential dangerous consequences for patients, including aggressive immunosuppressive therapies.
Update on novel multiple sclerosis treatments: from dismal defeat to scintillating success.
Cree B, Hartung HP
Curr Opin Neurol · 2025 Jun · PMID 40138388 · Full text
PURPOSE OF REVIEW: To review novel multiple sclerosis (MS) therapies currently in clinical trials. RECENT FINDINGS: Sixty-seven clinical trials were selected and grouped into the following categories: Bruton's tyrosine k...
PURPOSE OF REVIEW: To review novel multiple sclerosis (MS) therapies currently in clinical trials. RECENT FINDINGS: Sixty-seven clinical trials were selected and grouped into the following categories: Bruton's tyrosine kinase inhibitors, remyelinating therapies, immunomodulators, B cell therapies, supplements/microbiome influencers, and cell-directed therapies. Important findings include tolebrutinib's successful trial in nonrelapsing secondary progressive MS that slowed CDP compared to placebo and simvastatin's failure to show an effect on disability in its phase 3 trial. SUMMARY: Multiple strategies are being investigated in MS to address progressive disability, myelin repair, neural protection and treatment refractory disease. Some of these strategies have successfully completed clinical trials giving hope that some of the most vexing aspects of MS will soon have new treatment options.
Advances in neuroimaging of multiple sclerosis.
Rocca MA, Preziosa P, Filippi M
Curr Opin Neurol · 2025 Jun · PMID 40104925 · Publisher ↗
PURPOSE OF REVIEW: To summarize recent advancements in understanding multiple sclerosis (MS) pathophysiology, predicting disease course, and monitoring treatment responses using MRI. RECENT FINDINGS: Paramagnetic rim les...
PURPOSE OF REVIEW: To summarize recent advancements in understanding multiple sclerosis (MS) pathophysiology, predicting disease course, and monitoring treatment responses using MRI. RECENT FINDINGS: Paramagnetic rim lesions (PRLs) are highly specific to MS and clinically relevant. Detected from the earliest disease phases, PRLs aid in distinguishing MS from other conditions, improving diagnostic accuracy. Moreover, PRLs are associated with more severe disability and measures of brain damage and may predict disease progression. Similarly, slowly expanding lesions (SELs) are associated with more severe disability and predict a more severe disease course. Disease-modifying therapies have limited effectiveness in reducing PRLs or SELs. Choroid plexus (CP) enlargement is associated with structural brain damage and clinical disability and predicts disease evolution. Enlarged perivascular spaces (ePVS) suggest microangiopathic changes rather than direct MS-related inflammation. Glymphatic dysfunction, evaluated using diffusion tensor image analysis along the perivascular space, emerges early in MS and correlates with disability, cognitive impairment, and structural brain damage. Aging and comorbidities exacerbate MS-related damage, complicating diagnosis and treatment. Emerging technologies, such as brain-age paradigms, aim to disentangle aging from MS-specific neurodegeneration. SUMMARY: Advances in MRI have highlighted the clinical significance of chronic inflammation and glymphatic dysfunction as early contributors to MS progression as well as the interplay between aging, comorbidities and MS.
Multiple sclerosis in China: the current state of diagnosis and management.
Jia D, Shi FD, Jiang W
Curr Opin Neurol · 2025 Jun · PMID 40104913 · Publisher ↗
PURPOSE OF REVIEW: This comprehensive overview summarized the latest advances of multiple sclerosis (MS) in China, including the diagnostic and treatment challenges, research and future directions under health policy rec...
PURPOSE OF REVIEW: This comprehensive overview summarized the latest advances of multiple sclerosis (MS) in China, including the diagnostic and treatment challenges, research and future directions under health policy recommendations. RECENT FINDINGS: Given the rising prevalence of MS in China during the past decades, it has emerged as a significant public health concern due to the extensive population and pronounced disparities between urban and rural areas. The clinical manifestations of MS patients in China can be various due to the nation's diversity and evolving environmental factors. Advances in diagnostic practices, including the advances under 7T MRI radiological assessments, have enhanced the precision of MS diagnosis. Despite the introduction of disease-modifying therapeutic agents and the support of healthcare policies offering patients a wider range of treatment options, multiple ongoing research efforts and clinical trials will provide additional evidence. The ongoing China National Registry of Neuro-Inflammatory Diseases study (NCT05154370) holds promise for further enhancing the management of MS patients in China. SUMMARY: Improved recognition and management of MS in China have been facilitated, encompassing both prompt diagnosis and diverse treatment options. Simultaneously, research efforts and large-scale cohort studies have significantly advanced the overall status in this field.
Persistent aura without infarction.
Severino M, Green MW
Curr Opin Neurol · 2025 Jun · PMID 40062461 · Publisher ↗
PURPOSE OF REVIEW: The scope of this review is to discuss persistent aura without infarction, a rare, highly disabling, yet apparently benign clinical condition, straddling neurology, neuro-ophthalmology, and psychiatry,...
PURPOSE OF REVIEW: The scope of this review is to discuss persistent aura without infarction, a rare, highly disabling, yet apparently benign clinical condition, straddling neurology, neuro-ophthalmology, and psychiatry, whose differential diagnosis is essential for an appropriate therapeutic approach and to avoid clinical complications. Here we attempt to report on the available literature, trying to present a summary, despite the scarcity of available literature. RECENT FINDINGS: Persistent aura without infarction is a diagnostic challenge, likely caused by cortical spreading depression and vasoconstriction, whose clinical features are not always easy to pigeonhole into the available diagnostic criteria. The diagnosis requires the exclusion of cerebral and retinal infarction, structural changes in the brain, epilepsy, and psychiatric symptoms. Triptans may be deleterious, anticoagulants are not indicated, and therapy with acetazolamide, valproic acid, zonisamide, furosemide, cortisone, and ketamine may be beneficial. SUMMARY: Persistent aura without infarction is a challenging diagnosis. However, an approach using zonisamide and ketamine might be beneficial. Randomized and controlled clinical trials are required for a better comprehension of the aetiopathogenesis and therapeutic approach.
Tuberculosis of the central nervous system: current concepts in diagnosis and treatment.
Garg RK
Curr Opin Neurol · 2025 Aug · PMID 40047235 · Publisher ↗
PURPOSE OF REVIEW: The outcome of central nervous system (CNS) tuberculosis has shown little improvement over several decades, with diagnosis remaining unconfirmed in nearly half of the cases. This review highlights curr...
PURPOSE OF REVIEW: The outcome of central nervous system (CNS) tuberculosis has shown little improvement over several decades, with diagnosis remaining unconfirmed in nearly half of the cases. This review highlights current insights and advancements in the diagnosis and treatment of CNS tuberculosis. RECENT FINDINGS: Miliary pulmonary tuberculosis is often linked to CNS tuberculosis and is associated with a worse prognosis. Complications, such as, optochiasmatic arachnoiditis, strokes, and transverse myelitis severely affect prognosis and quality of life. Nearly half of tuberculous meningitis patients exhibited impaired cognition. Diagnosing CNS tuberculosis is challenging because of the low accuracy of standard tests. Advanced techniques like metagenomic and nanopore sequencing enhance detection but are hindered by high costs and limited access. Treatment outcomes remain suboptimal but approaches such as higher drug doses, novel medications, and host-directed therapies are being explored. Drug-resistant tuberculous meningitis is increasingly recognized, posing significant challenges to both diagnosis and treatment. Artificial intelligence (AI) enhances care by enabling early diagnosis, disease monitoring, and personalized treatments, improving outcomes. SUMMARY: CNS tuberculosis diagnosis faces challenges due to limited sensitivity and delayed results of available tests. Treatments remain suboptimal, with multidrug-resistant cases posing high mortality risks. AI aids in early diagnosis and personalized care.
Gauging and controlling excitability in cortical disorders.
Friedrichs-Maeder C, Lepeu G, Baud MO
Curr Opin Neurol · 2025 Apr · PMID 39960270 · Publisher ↗
PURPOSE OF REVIEW: Cortical excitability, defined as the cortex's responsiveness to incoming stimuli, is a fundamental concept in neuroscience and a targetable mechanism for controlling brain dysfunctions such as epileps...
PURPOSE OF REVIEW: Cortical excitability, defined as the cortex's responsiveness to incoming stimuli, is a fundamental concept in neuroscience and a targetable mechanism for controlling brain dysfunctions such as epilepsy, as well as other neurological and psychiatric disorders. In this review, we delineate the boundaries between physiological and pathological excitability, highlighting recent theoretical, experimental, and translational advances relevant to human brain disorders. Specifically, we describe the dynamic regulation of cortical excitability and propose practical means to monitor its known fluctuations as to guide therapeutic interventions. RECENT FINDINGS: From a conceptual standpoint, the last decade of research on cortical excitability has benefited from dynamical systems theory, which studies the behavior of nonlinear systems (here, the cortex) and their resilience to perturbations in different conditions (here, variable excitability). We review how fundamental relationships between excitability and resilience were verified in the brain in a series of recent studies. We also review natural fluctuations in cortical excitability, and how these may open windows of vulnerability for the expression of cortical dysfunctions. We then turn to the practicalities of measuring and monitoring cortical excitability, a latent variable that must be actively probed. SUMMARY: Practical means for gauging cortical excitability likely have broad applicability. To enable new developments in clinical practice, a principled design of pharmacological and neurostimulation therapies must leverage current understanding of cortical dynamics.
Neuroinflammation and immunometabolism in neurodegenerative diseases.
Lonkar N, Latz E, McManus RM
Curr Opin Neurol · 2025 Apr · PMID 39936491 · Publisher ↗
PURPOSE OF REVIEW: Immunometabolism is an emerging field of research investigating the ability of immune cells to modulate their metabolic activity for optimal function. While this has been extensively examined in periph...
PURPOSE OF REVIEW: Immunometabolism is an emerging field of research investigating the ability of immune cells to modulate their metabolic activity for optimal function. While this has been extensively examined in peripheral immune cells like macrophages, only recently have these studies been extended to assess the immunometabolic activity of microglia, the innate immune cells of the brain. RECENT FINDINGS: Microglia are highly metabolically flexible and can utilize different nutrients for their diverse functions. Like other immune cells, they undergo metabolic reprogramming on immune stimulation and in inflammatory, neurodegenerative conditions such as Alzheimer's disease (AD). In recent years, researchers have looked at the intricate mechanisms that modulate microglial activity and have uncovered key links between altered metabolism, neuroinflammation, and the involvement of disease-associated risk genes. SUMMARY: This review highlights the recent studies that have significantly contributed to our understanding of the metabolic dysregulation observed in activated microglia in conditions such as AD, unveiling novel targets for therapeutic intervention.
SEEG in 2025: progress and pending challenges in stereotaxy methods, biomarkers and radiofrequency thermocoagulation.
Ryvlin P
Curr Opin Neurol · 2025 Apr · PMID 39927419 · Full text
PURPOSE OF REVIEW: Technological innovations and clinical research in SEEG have dramatically increased with its worldwide dissemination. In this review, we summarize the main advances in the field from the last 5 years....
PURPOSE OF REVIEW: Technological innovations and clinical research in SEEG have dramatically increased with its worldwide dissemination. In this review, we summarize the main advances in the field from the last 5 years. RECENT FINDINGS: Several large series and meta-analyses have provided consistent data regarding a lower risk of serious complications with SEEG as compared to sub-dural grids, while some studies also suggest a greater diagnostic value. The safety and precision of SEEG partly depends on the type of vascular imaging and method of implantation, with some series suggesting that MR angiography might not provide an optimal delineation of electrode-vessel conflicts and that frameless stereotaxy lacks precision. Noninvasive frame coupled with robot-guided implantation might offer the best precision/invasiveness tradeoff. Small series suggest that SEEG can be safely performed from the age of 16 months, and that adding electrodes during SEEG often prove beneficial. Transhemispheric electrodes targeting the mesial frontal structures, bilaterally, proved safe and informative. Several interictal and ictal biomarkers of the epileptogenic zone have been investigated. Although high-frequency oscillations (HFOs) remain a biomarker of interest, a randomized controlled trial failed to demonstrate its diagnostic value against spikes. Furthermore, other interictal biomarkers proved to better correlate with the epileptogenic zone than HFOs rate, including spike-gamma and spike-ripples. Ictal biomarkers of interest include the so-called chirp and epileptogenic zone fingerprint. Overall, recent data suggest that high-frequency activities are not a mandatory feature of interictal and ictal biomarkers of the epileptogenic zone. Radiofrequency thermocoagulation (RFTC) performed during SEEG investigation have also progressed, with some authors reporting spectacular rates of seizure freedom in patients with localized epileptogenic lesion but also mesial temporal sclerosis. However, a systematic assessment of memory and mental health demonstrated the presence of altered memory and psychiatric complications in a significant proportion of mesial temporal lobe RFTC. SUMMARY: Progress has been made in the technology and methods used to perform SEEG and RFTC, with the view to increase safety and effectiveness. Several interictal and ictal biomarkers appear promising but still face challenges in their validation and implementation in clinical practice. Future research requires harmonization in the concepts of the seizure onset and epileptogenic zones, and prospective pathology-specific studies.
Epilepsy in low- to middle-income countries.
Sen A, Newton CR, Ngwende G
Curr Opin Neurol · 2025 Apr · PMID 39927414 · Full text
PURPOSE OF REVIEW: Epilepsy disproportionately affects those in low- and middle-income countries (LMICs) where diagnostic and treatment gaps persist.We highlight key recent developments and showcase practical opportuniti...
PURPOSE OF REVIEW: Epilepsy disproportionately affects those in low- and middle-income countries (LMICs) where diagnostic and treatment gaps persist.We highlight key recent developments and showcase practical opportunities to improve epilepsy care in resource limited settings. RECENT FINDINGS: In LMICs, cultural, socioeconomic and infrastructural factors drive the epilepsy treatment gap. Robust implementation of the WHO Intersectoral Global Action Plan (WHO IGAP) and Mental Health Gap Action Program (mhGAP), for example, will reduce the epilepsy education gap. Engaging traditional healers and other key community leaders should lessen stigma. The Epilepsy Diagnostic Companion, a culture specific tool that helps identify convulsive seizures, can expedite epilepsy diagnosis at primary care level. Novel, robust 3-D printable EEG headsets prototypes that can be deployed in remote rural communities have been piloted with encouraging results. Levetiracetam has been added to the WHO Essential Medicines List (EML), paving way to safer, less teratogenic antiseizure medications (ASMs). Epilepsy surgery programs in carefully selected patients potentially offer cheap, effective and potentially curative treatments, including in LMICs. SUMMARY: Apps, EEG prototypes, better access to ASMs and implementation of WHO iGAP offer current, tangible opportunities to improve epilepsy care in LMICs. Bidirectional learning must be facilitated to also help hard to reach communities in high-income settings.
State-of-the-art gene therapy in epilepsy.
Walker MC
Curr Opin Neurol · 2025 Apr · PMID 39917784 · Full text
PURPOSE OF REVIEW: Gene therapy in epilepsy has undergone a rapid expansion in recent years. This has largely been driven by both advances in our understanding of epilepsy genetics and mechanisms, and also significant ad...
PURPOSE OF REVIEW: Gene therapy in epilepsy has undergone a rapid expansion in recent years. This has largely been driven by both advances in our understanding of epilepsy genetics and mechanisms, and also significant advances in gene therapy tools, in particular safe and effective viral vectors. Epilepsy remains an ideal target disease for gene therapy and this review highlights recent developments in this area. RECENT FINDINGS: There have been continued advances in the development of antisense oligonucleotide therapies to knock down genes in the treatment of monogenic epilepsies with some now entering clinical trial. However, the greatest recent advances have been in vector gene therapy, which offers a more permanent solution by delivering therapeutic genes directly to the brain as a one-off therapy. In particular, there has been a growth in methods that target focal epilepsy. Such promising approaches close to or in clinical trial include expressing NPY and its Y2 receptor, knocking-down GluK5, a kainate receptor subunit, and the over-expression of Kv1.1, an endogenous potassium channel.In the future, it is likely that we will take advantage of approaches of regulating more precisely network excitability by using methods such as optogenetics, designer receptors exclusively activated by designer drugs (DREADDs), 'inhibitory' glutamate receptors activated by excessive glutamate spill-over, and activity-dependent promoters, which target gene expression to the 'hyperactive' neurons. SUMMARY: Gene therapies offer a novel approach to the treatment of not just genetic epilepsies but any form of epilepsy and may in the future offer an alternative to drug and surgical therapies, allowing more precise, permanent and targeted treatment with fewer adverse effects.
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