共找到 20 条结果
Antithrombotic guidelines for secondary stroke prevention are derived predominantly from Western populations, yet East Asian patients exhibit markedly higher cytochrome P450 2C19 (CYP2C19) loss-of-function allele prevalence (50%-60% vs ~25% in Europeans) - polymorphisms essential for clopidogrel bioactivation - potentially generating population-specific cardiovascular risks not captured in Western-derived recommendations. To characterise the 100-day cardiovascular safety and effectiveness of antithrombotic regimens in East Asian ischaemic stroke patients and to develop a pharmacogenomically informed clinical risk prediction model. Nationwide retrospective cohort study. We analysed 5746 adults from Taiwan's National Health Insurance Research Database (2011-2020) stratified by antithrombotic regimen initiated within 48 h of confirmatory neuroimaging. Primary outcomes - recurrent ischaemic stroke, haemorrhagic stroke, acute myocardial infarction, heart failure and all-cause mortality - were assessed over 100 days. Multivariable Cox regression, propensity score matching, inverse probability weighting, Fine-Gray competing risks models, E-value bias quantification and negative control outcome analysis were applied. The East Asian Post-Stroke Antithrombotic Risk (EPSAR) score was developed incorporating age, sex, comorbidities and treatment regimen. Dual antiplatelet therapy (DAPT; aspirin plus clopidogrel) was associated with a 17.2-fold increased acute myocardial infarction risk versus aspirin monotherapy (95% confidence interval (CI) 5.61-52.7; number needed to harm 14). This signal was robust across all analytical approaches (propensity-matched hazard ratio (HR) 11.8; inverse probability of treatment weighting HR 13.4; competing-risks subdistribution HR 14.8) and yielded an E-value of 33.4, substantially exceeding the strength of known clinical confounders. Warfarin-containing regimens conferred markedly elevated haemorrhagic stroke risk (HR 7.11-8.77). Aspirin monotherapy demonstrated a 94% all-cause mortality reduction versus no treatment. Negative control outcomes showed no systematic bias (joint test p = 0.98). The EPSAR model achieved a C-statistic of 0.78 (95%CI 0.72-0.84). DAPT is associated with unexpected myocardial infarction risk in East Asian stroke patients, consistent with CYP2C19-mediated pharmacogenomic vulnerability. These findings challenge the universal applicability of Western-derived guidelines and support integration of pharmacogenomic risk stratification into antithrombotic prescribing for East Asian populations. Not applicable (observational study). Are standard blood thinners safe for everyone after a stroke? A study on the unexpected heart attack risks of combined therapies in East Asian patients Stroke is a leading cause of death and disability worldwide, and preventing a second stroke is a critical goal of medical care. Doctors commonly prescribe blood-thinning medications after stroke, with aspirin being the standard first choice. In recent years, combining aspirin with a second blood-thinning drug called clopidogrel – a strategy known as dual antiplatelet therapy – has gained wider use, particularly following influential clinical trials conducted in Asian patient populations. However, a problem rarely discussed in clinical guidelines is that roughly half of all East Asian people carry a common genetic variant that prevents their bodies from properly converting clopidogrel into its active form. This means the drug may not work as intended in a substantial proportion of patients across China, Taiwan, Japan, Korea, and other East Asian countries – a proportion far higher than in Western populations. Using Taiwan’s national health insurance database, which covers nearly the entire population of 23 million people, we studied over 5,700 patients hospitalised for acute ischaemic stroke or transient ischaemic attack between 2011 and 2020. We compared outcomes across different antithrombotic treatment groups over 100 days following the stroke event. Our most striking finding was that patients receiving dual antiplatelet therapy – aspirin plus clopidogrel – experienced a 17-fold higher rate of acute heart attacks compared with patients receiving aspirin alone. This finding remained consistent when we applied multiple statistical methods designed to rule out alternative explanations. Patients receiving warfarin-based regimens also faced substantially higher risks of bleeding into the brain. By contrast, aspirin monotherapy was associated with a major reduction in mortality compared with no treatment. We developed a practical clinical tool – the EPSAR score – that enables doctors to identify which post-stroke patients are at highest risk of heart attack from combination therapy, using information already available at the bedside. These findings suggest that antithrombotic treatment guidelines may need to be revised to account for the genetic and biological differences between East Asian and Western populations, moving toward more personalised, precision medicine approaches to stroke care.
Understanding and enhancing neural recovery in disorders of consciousness (DoC) remains a critical challenge in clinical care. Clinical scales such as the Coma Recovery Scale-Revised (CRS-R) are essential, but reflect behavioral responsiveness and may not fully capture subtle neurophysiological changes. Transcranial direct current stimulation (tDCS) has shown promise, yet objective biomarkers to assess treatment response are needed. This proof-of-concept study explores the feasibility and sensitivity of combining a compact single-channel EEG with noninvasive brain stimulation to assess changes in neural reactivity in individuals with DoC. Pilot observational study with DoC patients undergoing intervention; healthy controls were assessed to provide a physiological reference benchmark for interpreting mismatch negativity (MMN) responses and assess the specificity of EEG biomarkers relative to DoC patients. Six DoC patients underwent a 2-week open-label anodal tDCS protocol targeting the left dorsolateral prefrontal cortex. Neural activity was tracked using a compact three-electrode EEG alongside traditional 19-electrode EEG. To capture treatment-induced changes, three complementary biomarkers were analyzed: MMN, reflecting pre-attentive auditory discrimination function; Beta oscillatory activity, associated with global attentional processes; and L1, a machine-learning-derived biomarker of cognitive engagement. CRS-R, auditory event-related potentials, and EEG-based machine learning biomarkers were recorded at baseline and immediately post-intervention. Healthy controls underwent the same baseline EEG assessments without receiving stimulation. MMN, Beta, and L1 demonstrated task-related modulation in healthy participants across cognitive load levels. In DoC patients, changes were observed following tDCS in MMN, Beta activity, and L1 as well, with patients demonstrating complex heterogeneous response patterns. Two patients showed behavioral improvement (CRS-R), while others exhibited increased EEG reactivity without corresponding behavioral gains. These findings highlight the feasibility and potential value of integrating compact EEG systems with neuromodulation protocols to monitor neural reactivity in DoC patients, with the potential to inform and refine tDCS treatment strategies over time. NIH Clinical Trials Registry number: NCT04614792 (https://clinicaltrials.gov/study/NCT04614792). Detecting brain responses after stimulation in patients with disorders of consciousness using single-channel EEG This study explored whether a single-channel EEG device can detect changes in brain activity in patients with disorders of consciousness (DoC), such as vegetative state or minimally conscious state. These patients are often unable to communicate, making it difficult to assess brain function using behavior alone. In this pilot study, patients received a 10-day course of noninvasive brain stimulation (tDCS). Brain activity was measured before and after the intervention using EEG. Healthy participants were also tested to provide a reference for typical brain responses. The results showed that EEG could detect changes in brain activity following the stimulation, even when patients’ clinical scores (based on behavior) remained unchanged. In particular, one EEG measure (called L1) was able to distinguish between resting state and active task engagement, suggesting it reflects whether the brain is responding to external stimuli. These findings suggest that EEG may help identify brain activity that is not visible through behavior alone, potentially improving the assessment and monitoring of patients with disorders of consciousness. Larger studies are needed to confirm these results.
Inhibition of terminal complement activation is an effective therapeutic strategy for acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG) and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD), but it increases the risk of invasive meningococcal infections. Consequently, vaccination against meningococcal serogroups A, C, W, Y, and B is mandatory for all patients receiving complement inhibitors. This article provides expert consensus recommendations for managing meningococcal vaccination in patients with NMOSD and gMG receiving complement-inhibiting therapies in Germany, Austria, and Switzerland. The timing and procedures of vaccination should be adapted to the underlying diagnosis and the individual risk of disease exacerbation in this population. In NMOSD, treatment often must begin promptly, particularly after an acute attack; in such cases, vaccination should be administered at treatment initiation together with antibiotic prophylaxis. By contrast, treatment urgency in gMG is typically lower, allowing vaccination to be completed in advance and thereby avoiding antibiotic exposure, which may worsen gMG symptoms. For both diseases, ceftriaxone is recommended as first-line therapy for suspected infection, rifampicin for prophylaxis, and either rifampicin or intramuscular ceftriaxone for post-exposure chemoprophylaxis. Patients should also carry a standby dose of ciprofloxacin for emergency self-administration at the first signs of meningitis, followed by immediate clinical evaluation. These recommendations should be reviewed regularly and updated as necessary to reflect emerging evidence and new vaccine options. How to prevent serious infections during treatment for NMOSD and myasthenia gravis Blocking terminal complement activation is an effective treatment for people with acetylcholine receptor antibody–positive generalized myasthenia gravis (gMG) and aquaporin-4 antibody–positive neuromyelitis optica spectrum disorder (NMOSD). However, this treatment increases the risk of serious meningococcal infections. For this reason, all patients receiving complement inhibitors must be vaccinated against meningococcal serogroups A, C, W, Y, and B. This article presents expert consensus recommendations on how to manage meningococcal vaccination in patients with NMOSD and gMG receiving complement-inhibiting therapies in Germany, Austria, and Switzerland. The timing and approach to vaccination should be adapted to the specific disease and to each patient’s risk of worsening symptoms. In NMOSD, treatment often needs to start quickly, especially after an acute attack. In these cases, vaccination should be given at the start of complement inhibitor therapy together with preventive antibiotic treatment. In contrast, treatment for gMG is usually less urgent. This often allows vaccination to be completed before therapy begins and helps avoid antibiotic use, which may worsen gMG symptoms. For both diseases, ceftriaxone is recommended as the first treatment if infection is suspected. Rifampicin is recommended for preventive antibiotic treatment, and either rifampicin or intramuscular ceftriaxone can be used after possible exposure to infection. Patients should also carry a standby dose of ciprofloxacin to take immediately if early signs of meningitis appear, followed by urgent medical evaluation. These recommendations should be reviewed regularly and updated as new evidence and vaccines become available.
Chimeric antigen receptor T (CAR-T) cell therapy has transformed outcomes for relapsed/refractory B-cell malignancies and is increasingly reshaping the therapeutic landscape of autoimmune disorders and solid tumors, offering curative potential where options were previously limited. Its broader deployment is, however, constrained by immune-mediated toxicities, chiefly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS spans a heterogeneous spectrum from mild aphasia and tremor to seizures, cerebral edema, coma, and death, and remains difficult to predict prospectively. As CAR-T platforms expand beyond CD19 malignancies, neurotoxicity phenotypes are also broadening beyond classical ICANS. In plasma cell dyscrasias, BCMA-directed CAR-T has been associated with delayed non-ICANS neurotoxicities, including movement and neurocognitive/behavioral symptoms, cranial nerve palsies, and peripheral neuropathic presentations. In parallel, early experiences with CAR-T and related immune effector therapies in autoimmune and neuroimmunologic diseases suggest distinct inflammatory contexts and potentially different neurotoxicity patterns, underscoring the need for indication-specific monitoring and attribution frameworks. Converging data implicate a multilayered pathophysiology involving systemic cytokine surges, disruption of the blood-brain barrier, endothelial dysfunction, and context-dependent trafficking of activated CAR-T cells and other immune effectors into the CNS with baseline neurological vulnerability and the peri-infusion inflammatory milieu likely modulating individual risk. Given the frequency of these complications, an active research effort is underway to identify clinical, functional, and biological signals that could predict and improve their management. However, most biomarkers remain investigational, lacking prospective validation and straightforward clinical utility. This review synthesizes current evidence on the epidemiology, mechanisms, and monitoring of ICANS and emerging non-ICANS syndromes, and offers a fresh perspective on integrated, multimodal risk models to enable more precise stratification and timely intervention across indications. Understanding brain side effects of CAR-T cell therapy: why they happen and how we can prevent them CAR-T cell therapy is a breakthrough treatment that can cure some blood cancers when all other options have failed. It works by reprogramming a patient’s own immune cells to recognize and destroy cancer cells. Despite these successes, many patients experience neurological side effects after receiving CAR-T cells. These effects, grouped under the term ICANS (immune effector cell-associated neurotoxicity syndrome), can range from mild confusion, tremors, or trouble speaking to more severe complications such as seizures, brain swelling, or even coma. Beyond this syndrome, these therapies can also cause other neurotoxic complications, including peripheral nervous system involvement and longer term cognitive impairment. Central neurotoxicity develops through several overlapping processes. The treatment triggers a strong release of inflammatory molecules that disrupts the blood–brain barrier, allowing inflammatory signals and immune cells to enter the brain. Once inside, brain support cells like astrocytes and microglia release substances that can damage or overstimulate nerve cells, leading to swelling and impaired brain function. Some blood vessel support cells in the brain (pericytes and vascular smooth muscle cells) may also display the CD19 marker, creating the possibility of direct, unintended damage that further weakens the blood–brain barrier. The biology behind other types of neurological dysfunction remains incompletely understood. Assessment of ICANS and other neurological complications after CAR-T cells combines bedside neurological testing, brain scans, electrophysiology testing, and sometimes spinal fluid analysis. Current treatments rely on rapid detection and anti-inflammatory medicines such as corticosteroids and biological therapies, including anti-interleukin treatments. Most cases improve with timely care, but severe ICANS can be life-threatening. Understanding these mechanisms may enable better prediction, safer therapy design, and more effective pr.
Patients with Parkinson's disease (PD) receiving device-aided therapies (DATs) frequently experience vitamin B depletion and nutritional challenges. However, the effects of continuous subcutaneous apomorphine infusion (CSAI) on vitamin B status and nutritional outcomes in advanced PD remain unclear. To evaluate the clinical effectiveness of CSAI and associated changes in vitamin B status, homocysteine (Hcy) levels and nutritional outcomes in patients with advanced PD. A prospective observational cohort study in a single centre. Thirty patients with advanced PD were enrolled between January 2023 and March 2025. Clinical, biochemical and nutritional assessments were performed at baseline and after 3 months. Motor outcomes included daily OFF hours, dyskinesia hours, Hoehn and Yahr stage and the Unified PD Rating Scale (UPDRS). Biochemical measures comprised serum vitamins B1, B6, B12, folate and plasma Hcy levels. Nutritional status was assessed using body weight, body mass index (BMI) and the Mini Nutritional Assessment-Short Form (MNA-SF). Thirty participants (mean age 68.5 ± 9.2 years; disease duration 12.0 ± 3.9 years; Hoehn & Yahr 3.7 ± 0.7) completed follow-up. After 3 months of CSAI, daily OFF hours, dyskinesia hours and UPDRS Part 4 scores decreased significantly (p < 0.05 for all). The oral levodopa daily dose was significantly reduced (p < 0.001). Serum vitamin B1 and B12 levels increased significantly, while Hcy levels showed a modest but significant reduction (p < 0.05). Body weight, BMI and total MNA-SF score remained unchanged (p > 0.05). However, MNA-SF categories shifted toward improved nutritional classification (p = 0.008). Adjunctive antiparkinsonian medications were significantly reduced, while levodopa remained universally prescribed. CSAI significantly reduced motor complications and oral levodopa exposure. Secondary analyses showed selective biochemical improvements with stable overall nutritional status. Findings should be interpreted considering the observational design, lack of control group and short follow-up. CSAI demonstrates significant improvements in motor performance and vitamin B status, along with stabilised nutritional and cognitive profiles among Advanced PD patients Patients with Advanced Parkinson’s disease (PD) are at risk of vitamin B deficiencies and other nutritional challenges, especially when receiving device-aided therapy (DAT). These risks are particularly noted in patients treated with levodopa-carbidopa intestinal gel infusion (LCIG). Continuous subcutaneous apomorphine infusion (CSAI) is an alternative treatment option, but its effects on vitamin B status and overall nutrition are not well understood. This study evaluated changes in clinical measures, rating scales, vitamin B levels, and nutritional outcomes in 30 patients over 3 months of CSAI treatment. After 3 months, patients showed significant improvements in motor symptoms. Daily levodopa doses were reduced, and both daily OFF hours and dyskinesia hours decreased significantly. Serum vitamin B1 and B12 levels increased significantly, while Hcy levels decreased slightly but significantly, suggesting an overall improvement in vitamin B status. Cognitive assessment and general nutritional measures, including body weight, body mass index (BMI), and Mini Nutritional Assessment-Short Form (MNA-SF) scores, showed no significant changes. However, the distribution of nutritional categories shifted modestly, with a small reduction in the proportion of patients classified as malnourished and a slight increase in those with normal nutritional status. Overall, CSAI therapy was associated with substantial improvements in motor complications and a significant reduction in oral levodopa exposure. There was a significant reduction in the use of most adjunctive antiparkinsonian medications, while levodopa therapy remained universally prescribed. At the same time, metabolic and nutritional parameters showed generally small-to-moderate changes over the short-term follow-up period. In summary, 3 months of CSAI treatment was associated with improved motor function and better vitamin B status in patients with advanced PD, whereas cognitive and general nutritional outcomes remained stable. These findings indicate that CSAI may offer metabolic benefits and warrant further investigation regarding its potential role in preventing nutritional deficiencies.
Hereditary spastic paraplegia (HSP) groups rare, clinically and genetically heterogeneous neurodegenerative disorders, characterized by progressive lower-limb spasticity and weakness. Over the past decades, diagnostic strategies have evolved from pure clinical assessment to the integration of molecular tools, with next-generation and long-read sequencing (LRS) substantially increasing diagnostic yield and refining genotype-phenotype correlations. Neuroimaging provides complementary information, especially in specific subtypes such as SPG11 and SPG15, supporting diagnosis and guiding testing. Treatment has historically focused on symptomatic care, including physiotherapy, antispastic agents, and botulinum toxin, with dalfampridine explored for gait improvement in selected patients. More recently, research has expanded into disease-modifying avenues, such as drug repurposing (e.g., statins in SPG5, menatetrenone in ALS2) and early gene-based interventions in ultra-rare subtypes. At the same time, advances in technology, ranging from quantitative imaging and digital gait analysis to induced pluripotent stem cell models and artificial intelligence, are beginning to influence both clinical management and trial design. This review traces the trajectory of HSP care from its historical foundations to present standards and emerging innovations, outlining how technological progress is shaping realistic prospects for future therapeutic strategies. Research in HSP from today to tomorrow Hereditary spastic paraplegia (HSP) refers to a group of rare neurological conditions that mainly affect the legs, causing stiffness (spasticity), weakness, and difficulty walking. For many years, treatment options were limited, focusing mainly on easing symptoms through physical therapy or medications that reduce muscle stiffness. Genetic testing was not widely available, and many people went undiagnosed. In recent years, science and medicine have made major progress in understanding and managing HSP. Thanks to advanced genetic technologies, doctors can now identify the specific gene changes that cause the condition in many patients. This has opened the door to more targeted and personalized treatments. For example, gene therapy and antisense oligonucleotides – two forms of genetic medicine – are being tested in clinical trials and have already shown promising results in some rare forms of HSP. In parallel, researchers are finding new ways to repurpose existing drugs to treat HSP more quickly and effectively. Digital health tools like wearable sensors and smartphone apps are also helping patients and doctors to track symptoms and responses to treatment in real time, even from home. This article explains how treatment for HSP is moving from a “one-size-fits-all” approach to more personalized care, tailored to each person’s unique genetic and clinical profile. It also highlights how new technologies—like artificial intelligence—are helping scientists understand disease better and design more precise therapies. Although many treatments are still under development, the latest breakthroughs are offering new hope for individuals and families living with HSP.
Acute attacks of aquaporin-4 antibody neuromyelitis optica spectrum disorder (AQP4-Ab NMOSD) are typically managed with intravenous methylprednisolone, with therapeutic plasma exchange (PLEX) reserved for severe episodes. Despite these interventions, a subset of patients fails to respond and may sustain significant neurological disability. Complement C5 inhibitors, currently approved for long-term relapse prevention, have recently gained attention as a potential rescue therapy by rapidly inhibiting the terminal complement cascade, thus preventing downstream astrocytic injury. We report three patients with AQP4-Ab severe optic neuritis refractory to IV methylprednisolone and PLEX who demonstrated significant clinical improvement following administration of C5 inhibitors during the acute attack phase. Case 1 (right optic neuritis) and Case 3 (bilateral optic neuritis) received eculizumab, achieving near-complete and complete recovery of visual acuity, respectively. Both patients subsequently transitioned to rituximab within 8 weeks after their fourth weekly eculizumab infusion, while on a moderate dose of prednisolone. Case 2 (left optic neuritis) received ravulizumab, achieving partial visual recovery, and was continued on maintenance ravulizumab. Meningococcal prophylaxis with penicillin V was administered for all three patients. A literature review identified 10 publications utilising C5 inhibitors as acute attack therapies, totalling 31 cases, including our present series. Of these, 30 patients (97%) experienced neurological improvement within 4 weeks, with 28 (90%) showing improvement within the first week. Complete or near-complete recovery was observed in 42% of patients, while 55% achieved partial recovery, and one patient (3%) had no recovery. Patients achieving complete or near-complete recovery received C5 inhibitors significantly earlier than those with partial or no recovery (median 15.0 vs 24.0 days from symptom onset, p = 0.010); an optimal analytical cutoff of 23 days was identified. Infections were uncommon with no severe infections reported. In conclusion, emerging evidence supports the use of C5 inhibitors for acute NMOSD attacks, but larger studies are needed to establish robust evidence and inform clinical practice. Using C5 inhibitor medication to treat severe attacks of neuromyelitis optica spectrum disorder (NMOSD) when standard treatments fail Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare condition where the immune system attacks the nerves in the eyes and spinal cord. Attacks are usually treated with high-dose steroids or plasma exchange (a blood-cleaning procedure). However, some patients do not improve and risk permanent disability. C5 inhibitors are medications approved to prevent future NMOSD attacks. Their role as an emergency “rescue” treatment to stop an active, severe attack is not yet widely established. We treated 3 NMOSD patients suffering from severe vision loss who had not improved after standard therapies. They were given a C5 inhibitor (eculizumab or ravulizumab) as rescue therapy. We also reviewed the medical literature, analysing a total of 31 patients who received this rescue treatment. All 3 of our new patients experienced vision improvements after receiving the C5 inhibitor. When combined with published cases, 30 of 31 patients (97%) showed neurological improvement. This recovery was rapid, with 90% showing signs of improvement within the first week. Overall, 42% achieved complete or near-complete recovery, while 55% achieved partial recovery. Importantly, treatment timing was critical: patients achieving complete or near-complete recovery received the C5 inhibitor significantly earlier (median 15 days after symptom onset) than those with partial or no recovery (median 24 days). Initiating treatment beyond 23 days was unlikley to result in favourable outcomes. No severe infections were reported, likely because preventative vaccines and antibiotics were used. These findings suggest C5 inhibitors may be an effective emergency option for severe NMOSD attacks, potentially preventing permanent disability when started early. Larger studies are needed to confirm these results and establish clear clinical guidelines.
The necessity and optimal duration of post-thymectomy immunoregulatory medication (IM) in myasthenia gravis (MG) remain unclear. This study aimed to evaluate whether IM is required after thymectomy in MG patients and to determine the appropriate duration of IM in patients without postoperative deterioration by comparing long-term clinical outcomes. This triple-center, retrospective study included 1248 MG patients who underwent thymectomy. Among these patients, we compared outcomes between 483 patients without post-thymectomy IM and 765 patients receiving IM. Efficacy outcomes included post-thymectomy deterioration and minimal manifestation status (MMS) at 1 year. Safety outcomes, tumor growth, and serious complications were assessed between groups. Subgroup analyses were performed in mild cases (Myasthenia Gravis Foundation of America clinical classification (MGFA) ⩽2a at discharge), patients receiving IM for >1 year, and patients receiving IM for >2 years. Propensity score matching (PSM) was conducted for validation. Relative to 438 MG patients underwent thymectomy with no-IM therapy, 756 thymectomized MG patients receiving concomitant IM showed significantly superior outcomes, including lower deterioration (hazard ratio (HR) = 0.44, adjusted p < 0.001), lower deteriorated MGFA class (adjusted coefficient = 0.94, p < 0.001), and higher odds of achieving MMS at 1 year (odds ratio = 2.06, adjusted p < 0.001). No significant differences were observed in tumor development (3 years: p = 0.78; 5 years: p = 0.27) or serious complications (p = 0.53). Similar trends were observed across subgroups. Among patients without postoperative deterioration, IM longer than 1 year reduced deterioration risk compared with ⩽1 year (HR = 0.67 (0.50-0.91), p = 0.01), whereas extending IM beyond 2 years offered no additional benefit (p = 0.137). PSM analysis confirmed these findings. Our real-world analysis of 1248 MG patients suggests that thymectomy alone is not sufficient to achieve satisfactory outcomes. Post-thymectomy IM is recommended for at least 1 year, while extending treatment beyond 2 years appears to offer no further advantage in patients without deterioration. A multiple center real-world study looking at whether and for how long patients with myasthenia gravis need to continue immuno regulatory medications after thymectomy surgery to prevent symptoms from returning Why was this study done? For patients with myasthenia gravis (MG)—a chronic condition that causes muscle weakness—undergoing surgery to remove the thymus gland (a procedure called thymectomy) is a common and effective treatment. However, a major question remains for doctors and patients after the operation: Is it necessary to continue using immunoregulatory medications, and if so, for how long? There is a critical balance to be struck. Stopping these medications too early could risk the disease symptoms returning. On the other hand, using them for longer than needed exposes patients to potential side effects, such as a higher risk of infections, without a clear benefit. Currently, there is no strong consensus on the best approach. Therefore, this study was conducted to obtain evidence for this important treatment decision for patients and their doctors. What did the researchers do? To answer this question, we conducted a tri-center study that looked back at the medical records of 1,248 MG patients who had a thymectomy. We specifically compared the long-term health outcomes of 483 patients who did not receive any immunoregulatory medication after surgery to 765 patients who did. We examined key outcomes, including whether the MG symptoms came back (deterioration), the patients’ clinical status one year after surgery, and important safety issues like the risk of developing tumors or other serious complications. To make sure our comparisons were fair, we used adequate statistical methods to account for differences between the patient groups, ensuring the results were robust and reliable. What did the researchers find? Patients who took immunoregulatory medications after thymectomy had significantly better outcomes compared to those who did not. Their risk of the disease returning was less than half. They were also twice as likely to achieve a state of minimal or no symptoms one year after the operation. Reassuringly, we found no evidence that taking these medications increased the risk of tumors or other serious complications over the study period. Furthermore, for patients who showed no signs of the disease returning after surgery, we found that continuing the medication for more than one year was significantly better at preventing future deterioration than stopping within the first year. However, a key finding was that extending the medication beyond two years did not provide enough benefit in preventing recurrence compared to stopping at the two-year mark. What do these findings mean? This study provides evidence that for MG patients, a thymectomy should not be considered a standalone cure. Continuing immunoregulatory medications for at least one year after surgery is crucial to effectively prevent the disease from returning. Importantly, the findings also suggest that for the many patients who remain symptom-free after surgery, continuing these medications for longer than two years may be unnecessary, allowing them to try reducing treatment and avoid potential long-term side effects. This evidence helps doctors and patients create more personalized, safer treatment plans.
T cells, genetically modified to express chimeric antigen receptors (CAR T), successfully used in hemato-oncologic malignancies, are showing promising and sustained benefits in refractory autoimmune neurological diseases, including Myasthenia Gravis, stiff-person syndrome, neuromyelitis optica, myositis, autoimmune neuropathies, and multiple sclerosis. Several reported patients with a steadily progressive disease and evolving disability unresponsive to available therapies, including rituximab and new biologics, after 2-3 months of treatment with CARs targeting CD19-positive, antibody-secreting, long-lived plasma cells, and plasmablasts exhibit impressive, long-lasting, and drug-free clinical improvements with the potential for immune reset shifting immunity to a healthy state without the need for continuing more immunotherapy cycles. The review discusses what the unmet needs are with the present neuroimmunotherapeutics pointing out the disease stage and patient subsets for which CAR T-therapy is most suitable highlighting that CAR T should be applied in the early stages of disability development when patients reach early-active/refractory status rather than waiting for very late disease progression when neurological deficits might be irreversible. The future trajectory of CAR T cells is also described as a promising means destined to change the present therapeutic algorithm in all neuro-autoimmunites, even offering a promising path toward a cure, pointing out that, in contrast to currently approved biologics that selectively target one immunoregulatory factor, CD19 CAR T cells exert effects even beyond B cells, cross the blood-brain barrier and lymphoid tissues, and expand as "living cells" to memory cells ensuring sustained long-term benefits. Key therapeutic uncertainties and practicalities are however highlighted, including the exact duration of CAR T-cell therapy-induced drug-free remissions, logistical challenges, economic limitations, and the need for extensive collaborative efforts with experts in specialized clinical centers. Why CAR T cells can change the future therapies in autoimmune neurological diseases Because at least 20-25% of patients with common autoimmune neurological diseases, like Myasthenia Gravis, Stiff-Person Syndrome, Neuromyelitis, Myositis, Chronic Autoimmune neuropathies or Multiple Sclerosis, do not adequately respond or have stopped responding to current therapies exhibiting progressive or permanent disability, there is a need for novel therapeutic approaches. For such patients with refractory disease, CAR T cells can reverse the ongoing cumulative disability offering even a path toward a cure, without the need for continuing immunotherapy cycles; CAR T-therapies exert these actions because they can travel within the brain and the lymph nodes being able to modify the disease-specific lymphocytes responsible for the immune process and, most importantly, can expand as “living cells” ensuring their long-term benefits. The study discusses how these unique properties of CAR T cells can change the future treatment armamentarium in patients with autoimmune neurological diseases poorly responding to available therapies; describes the most suitable timing CAR T cells should be used after disease progression has begun; and highlights certain current uncertainties, such as the exact duration of CAR T-induced remissions, and economic or logistical challenges.
Impending and manifest myasthenic crisis (MC) represent life-threatening neurological emergencies that require immediate intervention. Although eculizumab, a terminal complement C5 inhibitor, has established efficacy in generalized myasthenia gravis, most studies have focused on long-term outcomes, and its potential for rapid onset of effect in acute exacerbations has not been well evaluated. We retrospectively analyzed four acetylcholine receptor (AChR) antibody-positive patients (five acute episodes) who received eculizumab as emergency therapy between January 2024 and July 2025. All patients presented with impending or manifest MC; none had received intravenous immunoglobulin, plasma exchange, or neonatal Fc receptor (FcRn) inhibition within the preceding month. According to the Myasthenia Gravis Foundation of America classification, three patients had class IVb and one had class V. Triggers for exacerbation included COVID-19 infection (n = 2), puerperium (n = 1), PD-1 inhibitor exposure (n = 1), and common infection (n = 1). Within 48 h of eculizumab administration, Quantitative Myasthenia Gravis scores improved from 28.2 ± 4.8 to 15.0 ± 4.1, while Myasthenia Gravis Activities of Daily Living scores decreased from 16.8 ± 2.8 to 6.0 ± 4.3. Notable milestones achieved included arterial blood gas improvement within 7.5 h (one patient), nasogastric tube removal within 48 h (three patients), and successful extubation at 17 h (one patient). No treatment-related adverse events were observed. These preliminary findings suggest that eculizumab may be associated with rapid, temporally related clinical improvement within 48 h with a favorable short-term safety profile in AChR antibody-positive patients with impending or manifest MC, particularly those with complement activation triggers. Larger prospective studies with standardized short-term assessment protocols, including frequent neurological evaluations during the first 48 h, are warranted to further validate its efficacy and define its role as an emergency therapy in the acute management of myasthenic exacerbations. Using eculizumab as an emergency treatment for severe worsening of myasthenia gravis: early experience from four patients with five crises Myasthenia gravis (MG) is a rare disease in which the body’s immune system interferes with communication between nerves and muscles, leading to weakness in the eyes, face, arms, legs, and sometimes breathing muscles. In its most severe form, called “myasthenic crisis,” patients can lose the ability to breathe on their own and require urgent hospital treatment. Standard emergency treatments such as intravenous immunoglobulin (IVIG) and plasma exchange can be effective, but they may take several days to work, leaving patients dependent on ventilators or feeding tubes for longer. Eculizumab is a medication that blocks part of the immune system known as the complement pathway, which plays a role in damaging the muscle–nerve connection in MG. While eculizumab is approved for generalized MG, most studies have examined its long-term benefits. Much less is known about whether it can act quickly enough to help in emergency situations. In this study, we reviewed four patients with MG (five episodes of severe worsening) treated at our hospital who received eculizumab during an emergency crisis. Triggers included infections, pregnancy recovery, cancer immunotherapy, and COVID-19. Within 48 hours of receiving eculizumab, patients showed meaningful improvement in their muscle strength and daily activities. Some were able to breathe without a ventilator or have feeding tubes removed much sooner than expected. Importantly, no serious side effects were observed in the short term. Our findings suggest that eculizumab may provide rapid improvement in patients experiencing life-threatening MG crises, particularly when the immune system is strongly activated. However, this was a very small study, and more research in larger groups of patients is urgently needed to confirm its safety and effectiveness as an emergency therapy.
The treatment of juvenile myoclonic epilepsy (JME) is limited, with most patients requiring long-term medication and over half experiencing seizure recurrence upon drug withdrawal. As a third-generation antiseizure medication, brivaracetam (BRV) has emerged as a promising therapeutic option. Its efficacy has been investigated in focal epilepsies and genetic generalized epilepsies (GGEs), with promising results. This study aims to evaluate the safety and preliminary efficacy of BRV as an off-label initial monotherapy in patients with newly diagnosed JME, with a specific focus on the control of myoclonic seizures. A prospective, single-center, and observational study. This study prospectively enrolled drug-naïve patients with JME. All participants received BRV monotherapy. Clinical data were collected at baseline and after a 6-month follow-up period, including demographic characteristics, electroencephalography (EEG), cranial magnetic resonance imaging (MRI), and comprehensive neuropsychological assessments. Changes in seizure frequency, cognitive function, levels of anxiety and depression, sleep quality, and quality of life from baseline to the 6-month follow-up were analyzed and compared. A total of 19 patients were included with a mean age of 20.26 ± 6.88 years (median: 18, interquartile range: 8), and a male-to-female ratio of 12:7. The average age of onset was 14.58 ± 3.42 years, and the average duration of epilepsy prior to BRV treatment was 5.71 ± 7.40 years (median: 2, interquartile range: 5). The mean frequency of myoclonic seizures at baseline was 38.79 ± 45.60 times per month (median: 10, interquartile range: 86). Eighteen patients (94.73%) experienced both generalized tonic-clonic seizures (GTCS) and myoclonic seizures, one patient only experienced myoclonic seizures, The MRI findings were negative in all patients (100%). The EEG of all patients at baseline was abnormal, revealing 3-5.5 Hz generalized spike-and-wave or polyspike-and-wave discharges. At the 6-month evaluation, all patients achieved seizure-free status (p < 0.001), neuropsychological assessments also demonstrated significant improvement, including Montreal Cognitive Assessment (MoCA; p < 0.001), Hamilton Anxiety Scale (HAMA; p < 0.001), Hamilton Depression Scale (HAMD; p < 0.001), Pittsburgh Sleep Quality Index (PSQI; p < 0.001), and Quality of Life in Epilepsy-31 (QOLIE-31; p < 0.001). Only one patient complained of poor sleep after BRV administration. This study suggests that BRV may offer promising efficacy, specifically in controlling myoclonic seizures and favorable tolerability as an off-label initial monotherapy for JME patients. While the evaluation of efficacy against GTCS requires longer follow-up, our findings support the potential of BRV as a therapeutic option for JME. Further randomized controlled trials are warranted to validate these observations. Is brivaracetam effective and safe as the initial monotherapy for patients with juvenile myoclonic epilepsy? Why was the study done? The treatment of juvenile myoclonic epilepsy (JME) is limited, with most patients requiring long-term medication and over half experiencing seizure recurrence upon drug withdrawal. Brivaracetam (BRV) has shown promising therapeutic potential in focal epilepsies and genetic generalized epilepsies (GGEs). What did the researchers do? This study evaluated the efficacy and safety of BRV as the initial monotherapy in patients with JME in clinical practice. What did the researchers find? A total of nineteen patients were included. Following treatment with BRV, all patients achieved seizure-free status (p<0.001), neuropsychological assessments also demonstrated significant improvement, including Montreal Cognitive Assessment (MoCA) (p<0.001), Hamilton Anxiety Scale (HAMA) (p<0.001), Hamilton Depression Scale (HAMD) (p<0.001), Pittsburgh Sleep Quality Index (PSQI) (p<0.001), and Quality of Life in Epilepsy-31 (QOLIE-31) (p<0.001). Only one patient complained of poor sleep. What do the findings mean? This study suggests that BRV may offer promising efficacy and tolerability as an initial monotherapy for JME, supporting its potential as a first-line treatment option. Further randomized controlled trials involving larger cohorts and extended follow-up periods are required to validate these findings.
Spinal dural arteriovenous fistula (SDAVF) is an important cause of venous congestive myelopathy, as timely treatment offers the potential for neurological recovery. However, it is sometimes misdiagnosed when presenting with atypical intracranial or brainstem lesions. Although venous congestion in SDAVFs typically develops adjacent to the shunting site, altered venous outflow dynamics occasionally result in remote parenchymal involvement. We present a case of lower cervical SDAVF manifesting as a remote medullary lesion mimicking area postrema syndrome. Subsequent spinal imaging and digital subtraction angiography revealed a right C6 SDAVF with cranially directed venous drainage. Fusion imaging of three-dimensional rotational angiography and anatomical MRI delineated the venous outflow bottleneck with abrupt focal narrowing at the cerebellomedullary fissure, which likely served as a morphological bottleneck contributing to preferential medullary congestion. The fistula was successfully treated via endovascular embolization, achieving complete angiographic obliteration and clinical recovery. A literature review was also conducted to characterize the clinical features and identify the common diagnostic pitfalls associated with these rare manifestations; however, the precise anatomical mechanisms for remote lesions remain elusive. This case highlights a potential anatomical mechanism wherein focal narrowing in the venous drainage pathway may predispose to atypical lesion localization. Furthermore, therapeutic considerations are discussed, emphasizing a stepwise treatment strategy in which endovascular obliteration is prioritized when the anatomy is favorable and surgical disconnection is reserved for refractory cases. Remote brainstem swelling caused by a arteriovenous fistula in the neck: identifying a venous “bottleneck” through advanced imaging A spinal dural arteriovenous fistula (SDAVF) is an abnormal connection between an artery and a vein near the spinal cord. This connection increases pressure in the veins, which usually causes swelling in the spine. However, in rare cases, the blood flows upward and causes swelling in the brainstem instead. We treated a patient whose fistula was located in the neck (cervical spine), but the resulting swelling was found higher up, in the brainstem. To understand why the swelling happened so far away from the fistula, we used a specialized 3D imaging technique. We discovered a “bottleneck”—a physical narrowing of the veins at the point where the brain meets the spine. This narrowing acted like a dam, forcing the high-pressure blood into the brainstem tissue. The fistula was successfully closed using an endovascular procedure, where medical glue was injected via a microcatheter to block the abnormal connection without the need for open surgery. The patient made a full recovery. Our findings help explain the anatomical reason for this unusual blood flow, which can help other medical teams diagnose this condition more effectively.
Intravenous thrombolysis (IVT) administered as a bridging therapy prior to endovascular thrombectomy (EVT) for acute ischemic stroke may increase the risk of hemorrhagic-transformation (HT). CT-perfusion (CTP) imaging enables quantitative assessment of ischemic core and penumbral tissue and may support individualized hemorrhagic risk stratification. To assess whether baseline CTP-defined ischemic core parameters are associated with parenchymal-hematoma type 2 (PH-2) following bridging IVT before EVT. Observational-cohort-study. Consecutive patients with large-vessel occlusion treated within 4 h of symptom onset at two tertiary stroke centers between 2017 and 2023 were analyzed. All patients underwent baseline CTP imaging. Outcomes were compared between patients treated with IVT plus EVT and those treated with direct-EVT. HT was assessed on 24-h follow-up noncontrast-CT using ECASS-2 criteria. Multivariable logistic regression was performed to identify independent predictors of PH-2. Among 398 patients (50.6% male), 180 received IVT + EVT (mean age 70.2 ± 15.0 years) and 218 underwent direct-EVT (69.5 ± 14.5 years). Baseline characteristics, workflow times, thrombectomy passes, and reperfusion rates were comparable. PH-2 was associated with higher mortality (43.8% vs 11.7%, p < 0.001) and worse 90-day functional outcome (median modified Rankin Score 4 (2-6) vs 3 (1-4), p = 0.002). Bridging-IVT was associated with higher PH-2 rates compared with direct EVT (6.1% vs 2.0%, p = 0.036), without increased symptomatic intracranial-hemorrhage. In sensitivity analyses, bridging-IVT was associated with higher PH-2 rates only in patients with any ischemic core (7.8% vs 1.5%, p = 0.014), core volume >10 mL (8.8% vs 0.8%, p = 0.004), and >20 mL (8.7% vs 1.3%, p = 0.03). Penumbral volume was not associated with PH-2. In multivariable analysis, any ischemic core (odds ratio (OR) 12.67, p = 0.02) and core volume >10 mL (OR 11.12, p = 0.034) independently predicted PH-2. Baseline CTP-defined ischemic core volume is strongly associated with severe HT following bridging intravenous alteplase prior to EVT and may inform individualized risk-benefit assessment of bridging therapy. CT perfusion scans can identify stroke patients at risk of serious bleeding after receiving clot-dissolving drugs before thrombectomy When someone has a major stroke caused by a large blood clot blocking blood flow in the brain, doctors have two main emergency treatments. One is giving a medicine through a vein (called “clot-busting” or thrombolysis) to help dissolve the clot. The other is a procedure called thrombectomy, where doctors physically remove the clot using a catheter. Sometimes, both treatments are given together, with the medicine given first while preparing for the procedure. A concern with clot-busting medicine is that it can raise the risk of bleeding in the brain, a complication that can make recovery worse or even be life-threatening. Today, many hospitals routinely perform advanced brain scans (called CT perfusion scans) that show how much brain tissue is already severely injured (the “core”) and how much could still be saved (the “penumbra”). In this study, nearly 400 patients who arrived at two large stroke centers within four hours of symptom onset were analyzed. About half received both the medicine and thrombectomy, and half had thrombectomy alone. The two groups were otherwise very similar. The researchers found that patients who received both treatments were more likely to develop a serious type of bleeding called “parenchymal hematoma type 2” – but only if their brain scans already showed damaged brain tissue (core). This higher bleeding risk was especially clear when the damaged core was larger than 10 milliliters. Importantly, the size of the at-risk but not yet dead tissue (penumbra) did not affect bleeding risk. These results suggest that clot-busting medicine may be safer in patients whose scans show little or no permanently damaged brain tissue, while those with larger damaged areas might do better with thrombectomy alone. Using advanced CT scans may help tailor treatment and avoid harmful side effects.
Leucine-rich glioma-inactivated 1 (LGI-1) antibodies are the second most common cause of autoimmune encephalitis, which is characterized by frequent seizures, memory loss, and psychiatric symptoms. Although most patients respond well to immunotherapy, treatment is often delayed or insufficient, resulting in a 14%-35% relapse rate and persistent neurological deficits. Therefore, exploring fast-acting and targeted therapies is crucial. To present a series of cases involving anti-LGI1 encephalitis treated with efgartigimod, and to assess the efficacy and safety of this therapeutic approach in managing this condition. A prospective, multicenter, and observational study. This study prospectively enrolled patients with anti-LGI1 encephalitis treated with efgartigimod and conducted a systematic review of the literature on the use of efgartigimod for anti-LGI1 encephalitis. The clinical outcomes before and 2 weeks after treatment were then compared. A total of eight patients and two additional cases from the literature were included in the study, with a mean age of 55.6 ± 15.88 years and a male-to-female ratio of 6:4. The predominant clinical manifestations among the patients included seizures, psychiatric and behavioral abnormalities, and memory decline. Following treatment with efgartigimod, the modified Rankin scale (p = 0.006; 95% confidence interval (CI) 2-2.5), Clinical Assessment Scale in Autoimmune Encephalitis (p = 0.008; 95% CI 2.5-9.5), and Mini-Mental State Examination scores (p = 0.042; 95% CI 0-14) significantly improved. In addition, a significant reduction was observed in both serum IgG levels (p < 0.001; 95% CI 4.66-6.81) and antibody titers (p = 0.004) post-treatment, indicating that the degree of antibody decline is negatively correlated with clinical severity. No adverse events were reported for any of the patients in this study. This study suggests that efgartigimod may offer promising efficacy and safety for patients with anti-LGI1 encephalitis. Further randomized controlled trials involving larger cohorts and extended follow-up periods are required to validate these findings. Is efgartigimod effective and safe for the treatment of anti-LGI1 encephalitis? Why was the study done?Anti-LGI1 encephalitis has been the second most common subtype of AE-related to anti-neuronal surface antibodies, resulting in significant neurological and psychiatric symptoms. Although most patients respond well to immunotherapy, prognosis remains poor for a minority of patients. Therefore, effective, targeted, and well-tolerant treatments for anti-LGI1 encephalitis are urgently needed. What did the researchers do?This study evaluated the efficacy and safety of efgartigimod as add-on therapy for patients with anti-LGI1 encephalitis in Beijing Tiantan Hospital and the First Affiliated Hospital of Zhengzhou University. What did the researchers find?A total of eight patients and two additional cases from the literature were included in the study. Following treatment with efgartigimod, there was a statistically significant improvement in scores on the modified Rankin scale (mRS, p = 0.006; 95% confidence interval (CI) 2 to 2.5), the Clinical Assessment Scale in Autoimmune Encephalitis (CASE, p = 0.008; 95% CI 2.5 to 9.5), and the Mini-Mental State Examination (MMSE, p = 0.042; 95% CI 0 to 14). Additionally, there was a significant reduction in both serum IgG levels (p < 0.001; 95% CI 4.66 to 6.81) and antibody titers (p = 0.004) post-treatment. No adverse events were reported in any of the patients in this study. What do the findings mean?This study highlights the therapeutic potential of efgartigimod in anti-LGI encephalitis, demonstrating rapid clinical improvement and well-tolerability. It should be noted that this study is limited by its small sample size. Further randomized controlled trials involving larger cohorts and extended follow-up periods are required to validate these findings.
A clinically significant proportion of patients experience early neurological deterioration (END) despite receiving dual antiplatelet therapy (DAPT) for acute ischemic stroke. It is crucial to identify this specific population for risk stratification and targeted intervention. To identify predictors for END after DAPT in acute ischemic stroke. We performed a post hoc analysis of the antiplatelet therapy in acute mild to moderate ischemic stroke (ATAMIS) trial. Patients who received DAPT (clopidogrel plus aspirin) in the ATAMIS trial were included, and classified into END and Non-END groups according to whether they experienced END. END was defined as an increase of ⩾2 points within 7 days from baseline on the National Institutes of Health Stroke Scale (NIHSS). Independent predictors were identified using multivariable logistic regression. Of the 1,122 patients with acute mild-to-moderate ischemic stroke treated with DAPT, 66 (5.9%) developed END within 7 days. Multivariable analysis identified three independent factors associated with increased END risk: a shorter time from symptom onset to antiplatelet initiation (adjusted odds ratio [aOR] per hour, 0.97; 95% CI, 0.95-0.99; p = 0.01), higher admission systolic blood pressure (aOR per mmHg, 1.01; 95% CI, 1.00-1.02; p = 0.047), and a stroke etiology of either small artery occlusion (aOR, 2.24; 95% CI, 1.29-3.89; p = 0.004) or cardioembolism (aOR, 28.36; 95% CI, 1.23-654.11; p = 0.04). Among patients with mild-to-moderate ischemic stroke receiving DAPT, key predictors of END include very early presentation, elevated systolic blood pressure at admission, and a nonlarge artery atherosclerosis etiology (small artery occlusion or cardioembolism). These findings highlight subgroups that may require intensified monitoring or adjunctive therapeutic strategies beyond standard DAPT. ClinicalTrials.gov Identifier: NCT02869009. Risk of experiencing neurological deterioration in the early stage after receiving dual antiplatelet therapy for patients who are diagnosed as acute ischemic stroke. A clinically significant proportion of patients experience early neurological deterioration (END) despite receiving dual antiplatelet therapy (DAPT) for acute ischemic stroke. Identifying risk factors for END in this specific population is crucial for risk stratification and targeted intervention. We performed a post hoc analysis of the Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke (ATAMIS) trial, focusing on patients who received DAPT (clopidogrel plus aspirin). The primary outcome was END within 7 days, defined as an increase of ⩾2 points from baseline on the National Institutes of Health Stroke Scale (NIHSS). Independent predictors were identified using multivariable logistic regression. Of the 1,122 patients with acute mild-to-moderate ischemic stroke treated with DAPT, 66 (5.9%) developed END within 7 days. Multivariable analysis identified three independent factors associated with increased END risk: a shorter time from symptom onset to antiplatelet initiation (adjusted odds ratio [aOR] per hour, 0.97; 95% CI, 0.95–0.99; p = 0.01), higher admission systolic blood pressure (aOR per mmHg, 1.01; 95% CI, 1.00–1.02; p = 0.047), and a stroke etiology of either small artery occlusion (aOR, 2.24; 95% CI, 1.29–3.89; p = 0.004) or cardioembolism (aOR, 28.36; 95% CI, 1.23–654.11; p = 0.04). Thus, among patients with mild-to-moderate ischemic stroke receiving DAPT, key predictors of END include very early presentation, elevated systolic blood pressure at admission, and a non-large artery atherosclerosis etiology (small artery occlusion or cardioembolism). These findings highlight subgroups that may require intensified monitoring or adjunctive therapeutic strategies beyond standard DAPT.
Plasma exchange (PE) is a therapeutic option for CNS demyelinating attacks unresponsive to corticosteroids, but the potential benefit of adding rituximab and IV immunoglobulins to PE (RTX-IVIG-PE), which has shown its efficacy and safety in other immune-mediated conditions, has not been investigated. We aimed to determine the overall effectiveness of PE in severe demyelinating attacks, identify predictors of response, and compare outcomes between standard PE and RTX-IVIG-PE protocols. Retrospective analysis of patients with CNS demyelinating attacks treated with PE between 2012 and 2023 across five Spanish hospitals. Clinical response was measured as an improvement or a complete recovery at discharge and 6 months. Uni- and multivariable logistic regression models were developed to identify predictors of PE response. A logistic regression analysis, after inverse probability of treatment weighting (IPTW), was performed to compare the outcome of attacks treated with standard PE and RTX-IVIG-PE. A total of 162 attacks in 150 patients (81 multiple sclerosis; 37 others acquired demyelinating syndromes; 27 neuromyelitis optica spectrum disorder; 5 myelin oligodendrocyte glycoprotein antibody-associated disease; 73% female; median age 43 years (interquartile range 33-52.75)) were analyzed. At discharge, 60% of all attacks showed clinical improvement, and 15% achieved complete recovery. At 6 months, these rates increased to 77% and 31%, respectively. Younger age, lower preattack Expanded Disability Status Scale, and treatment with RTX-IVIG-PE were independent predictors of complete recovery at 6 months. IPTW analysis showed that attacks treated with RTX-IVIG-PE (33) were associated with improvement (adjusted odds ratio (aOR) 5.4, p < 0.001) and complete recovery (aOR 4.55, p < 0.001) at 6 months compared to those treated with standard PE (129), without significant differences in the adverse event profile between the two protocols. PE improves the outcome of steroid-refractory CNS demyelinating attacks, and the addition of rituximab and IVIG to PE may increase the likelihood of long-term recovery. Improving recovery after severe inflammatory attacks of the brain and spinal cord: how combining plasma exchange with rituximab and immunoglobulins may lead to better long-term outcomes Severe inflammatory attacks affecting the brain, spinal cord, or optic nerves can cause sudden and serious disability in people with diseases such as multiple sclerosis and related conditions. These attacks are usually treated first with high-dose steroids, but some patients do not improve with this approach. In these situations, a treatment called plasma exchange is often used. Plasma exchange is a procedure that removes harmful antibodies and inflammatory substances from the blood. In this study, we looked at how well plasma exchange worked in people with severe attacks that did not respond to steroids. We also examined whether adding two additional treatments—rituximab (a drug that reduces certain immune cells) and intravenous immunoglobulins (protective antibodies from healthy donors)—could further improve recovery. We reviewed medical records from five hospitals in Spain and included 150 patients who experienced 162 severe attacks between 2012 and 2023. Most patients showed improvement after plasma exchange. About 6 out of 10 patients improved by discharge, and this increased to more than 3 out of 4 patients after six months. Importantly, recovery continued over time, meaning that some patients who did not improve immediately showed benefits months later. Patients who were younger, had less disability before the attack, and received the combined treatment with rituximab and immunoglobulins were more likely to recover fully. Those who received the combined treatment had a higher chance of both improvement and complete recovery six months after the attack compared with those who received plasma exchange alone. Importantly, adding these treatments did not increase the risk of serious side effects or infections. In summary, plasma exchange is an effective treatment for severe inflammatory attacks of the nervous system when steroids fail. Combining plasma exchange with rituximab and immunoglobulins may increase the chances of long-term recovery.
Converging lines of preclinical evidence support the neuroprotective properties of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in Parkinson's disease (PD). Nevertheless, results from randomized-controlled clinical trials (RCTs) remain conflicting. To assess the safety and efficacy of GLP-1 RAs in PD. Systematic review and meta-analysis of randomized placebo-controlled clinical trials. A systematic search of MEDLINE and Scopus databases was conducted on October 7, 2025, for randomized placebo-controlled clinical trials investigating GLP-1 RAs in adults with PD. Risk of bias was evaluated using the Cochrane Collaboration risk-of-bias (RoB2) tool. Four RCTs comprising 667 PD patients (377 receiving GLP-1 RAs) were included. Between baseline and end-of-treatment, no differences were observed in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score change between GLP-1 RA- and placebo-treated patients in either off-medication (standardized mean difference (SMD): -0.16; 95% CI: -0.64 to 0.32; p = 0.52) or on-medication states (SMD: -0.13; 95% confidence interval (CI): -0.51 to 0.25; p = 0.49). No significant differences were uncovered in other MDS-UPDRS subscores, Non-Motor Symptoms Scale, Montreal Cognitive Assessment, or Parkinson's Disease Questionnaire scores. The risk of serious adverse events and odds of treatment discontinuation were similar between groups, but GLP-1 RAs were associated with an increased risk of weight loss compared to placebo (risk ratio: 1.44; 95% CI: 1.04-1.99; p = 0.03). GLP-1 RAs were not associated with improvements in motor or non-motor domains of PD. However, robust preclinical evidence and promising findings in select subpopulations warrant further RCTs to evaluate their neuroprotective potential, prioritizing long-acting and brain-penetrant agents that effectively engage central GLP-1 circuits for PD treatment. The pre-specified protocol of the present systematic review and meta-analysis has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (registration ID: CRD420251008703). Efficacy and safety of glucagon-like peptide-1 receptor agonists in Parkinson’s disease: a systematic review and meta-analysis Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are medications approved for type 2 diabetes and obesity that have shown neuroprotective effects in preclinical models of Parkinson’s disease (PD). However, clinical trial results have been inconsistent. In this systematic review and meta-analysis, we evaluated the overall safety and effectiveness of GLP-1 RAs in people with PD by analyzing data from all available randomized placebo-controlled clinical trials. Our findings indicate that GLP-1 RAs do not lead to measurable improvements in motor symptoms, cognitive performance, or quality of life when compared to placebo. Although the risk of serious adverse events was similar between treatment and placebo groups, GLP-1 RAs were associated with an increased risk of weight loss and gastrointestinal adverse events. Despite the lack of demonstrated clinical benefit, strong preclinical evidence and exploratory signals in specific patient subgroups support the need for further high-quality trials, particularly with long-acting and brain-penetrant GLP-1 RAs in early-stage PD populations.
Current guidelines consider mechanical thrombectomy (MT) reasonable for M2 segment middle cerebral artery (MCA) occlusions within 6 h of symptom onset, yet the impact of delayed intervention in this population remains unclear. This study compared effectiveness and safety outcomes of MT performed in late (>6 h) versus early (⩽6 h) treatment windows in patients with acute primary embolic M2 occlusions. We retrospectively analyzed patients with primary embolic M2 occlusions treated with MT within 24 h of onset from the ARTISTA (A Registry for Thrombectomy In Stroke Therapy from Andalusia) registry (2017-2024) in Seville-Huelva, Spain. Outcomes compared between late and early treatment groups included good outcome (90-day modified Rankin Scale (mRS) 0-2 or return to prestroke mRS), futile recanalization (FR; 90-day mRS >2 despite successful recanalization), successful recanalization (modified Thrombolysis in Cerebral Infarction ⩾2b), and symptomatic intracranial hemorrhage (sICH). Multivariable logistic regression and inverse probability of treatment weighting (IPTW) analyses were performed to evaluate associations between treatment window and MT outcomes. Among 524 patients (median age 76, 48.3% women), 207 (39.5%) underwent MT in the late window. Late treatment showed numerically lower rates of good outcome (58.9% vs 64.4%) and higher rates of FR (37.8% vs 32.5%) and sICH (3.4% vs 3.2%), though none were statistically significant (all p ⩾0.211). Successful recanalization rates were nearly identical between the late and early windows (95.7% vs 95.6%; p = 0.970). IPTW-adjusted analyses also found no significant differences in good outcome (adjusted odds ratio (aOR), 0.82; 95% confidence interval (CI), 0.39-1.73; p = 0.600) or FR (aOR, 1.19; 95% CI, 0.56-2.50; p = 0.653) at 90 days. In this multicenter real-world cohort, MT performed beyond 6 h showed effectiveness and safety outcomes comparable to early-window intervention in patients with primary embolic MCA M2 occlusions. Does time still matter? Understanding how early and delayed thrombectomy compare in patients with M2 stroke When a blood vessel in the brain becomes blocked, restoring blood flow quickly is essential. Mechanical thrombectomy—a procedure in which doctors remove the clot directly—is commonly used for large-vessel strokes. However, for blockages in a smaller vessel called the M2 segment of the middle cerebral artery, current guidelines mainly support treatment within the first 6 hours after symptoms begin. Whether patients who arrive later can still benefit has remained uncertain. In this study, we examined real-world data from more than 500 patients in Spain who had an M2 stroke caused by an embolus. All patients received thrombectomy within 24 hours of symptom onset. We compared those treated early (within 6 hours) with those treated later (after 6 hours) to understand whether timing affected recovery or safety. We found that patients treated after 6 hours did not have worse outcomes than those treated earlier. Their chances of returning to independence were similar, as were the rates of successful restoration of blood flow. Importantly, the risk of complications—such as bleeding in the brain—was also comparable. Even after adjusting for age, stroke severity, and other medical factors, delayed treatment did not appear to reduce the potential benefit of thrombectomy. These findings suggest that, for carefully selected patients with M2 occlusions, performing thrombectomy after 6 hours may still be effective and safe. While more prospective research is needed, this study provides encouraging real-world evidence that could help guide clinical decisions and support broader treatment options for patients who arrive beyond the traditional time window.
Autoimmune (AI) comorbidities are common in people with multiple sclerosis (MS) and may complicate therapeutic management, particularly when dual immunosuppression is required. Cladribine, an immune reconstitution therapy approved for relapsing MS, has shown potential benefit in selected autoimmune disorders. To evaluate the prevalence of AI comorbidities in a large French MS cohort and explore the potential efficacy of cladribine in MS patients with concomitant autoimmune diseases. Retrospective multicenter registry analysis combined with a descriptive case series and literature review. Data were retrospectively extracted from the European Database for MS across five French tertiary MS centers. Adults with MS and documented autoimmune comorbidities were identified, including a subgroup treated with oral cladribine. In addition, eight detailed clinical cases of MS associated with autoimmune diseases treated with cladribine were reviewed to assess outcomes on both MS and the associated autoimmune condition. Among 11,410 people with MS, 901 had at least one autoimmune comorbidity, corresponding to a prevalence of 7.9 ± 0.25% (age 50.8 years), with a predominance of women. Of 385 cladribine-treated patients, 39 (10.1% ± 1.54%) had concurrent autoimmune disorders, although this proportion did not significantly differ from the overall cohort (p = 0.11). Eight cases involving ankylosing spondylitis (n = 3), psoriatic arthritis (n = 2), psoriasis (n = 1), rheumatoid arthritis (n = 1), and sarcoidosis (n = 1) were analyzed. Cladribine was consistently associated with MS stability, while efficacy on associated autoimmune conditions was variable, with more favorable outcomes observed in ankylosing spondylitis, psoriasis, and sarcoidosis. Autoimmune comorbidities affect approximately 8% of the French MS population and are more frequent in women. Cladribine may represent a useful therapeutic option in selected patients with concomitant autoimmune disorders, potentially limiting prolonged dual immunosuppression. Larger prospective studies are required to confirm efficacy and safety. OFSEP/EDMUS registry, ClinicalTrials.gov: NCT02889965. Cladribine as a possible treatment for MS with other autoimmune diseases A French study involving more than 11,000 people with multiple sclerosis (MS) found that around 8% also had another autoimmune disease, with women more commonly affected. Because treating both conditions can require multiple long-term immune-suppressing therapies, researchers explored whether cladribine, an approved MS treatment, could help control both diseases simultaneously. Among patients receiving cladribine, about 10% had an additional autoimmune disorder. Researchers closely reviewed eight patients with MS plus conditions including ankylosing spondylitis, psoriatic arthritis, psoriasis, rheumatoid arthritis, or sarcoidosis. The study found that MS remained stable in patients treated with cladribine. Some associated autoimmune conditions, especially ankylosing spondylitis, psoriasis, and sarcoidosis, also appeared to improve, although results were mixed for other diseases. Overall, the findings suggest that cladribine could be a useful treatment option for certain patients with both MS and autoimmune comorbidities, potentially reducing the need for multiple therapies. However, current evidence remains limited, and larger clinical studies are needed to confirm its safety and effectiveness for these additional autoimmune conditions.
Chronic subdural hematoma (CSDH) is an increasingly common disorder characterized by persistent accumulation of blood products and inflammatory exudate within the dural border cell (DBC) layer. Its pathogenesis represents a self-sustaining cycle of inflammation, pathological angiogenesis, and impaired resolution. Injury of the head, which may be traumatic or nontraumatic, initiates cleavage of the DBC layer, leading to fibroproliferative membrane formation mediated by collagen synthesis and TGF-β1/SMAD signaling. The resulting outer membrane develops fragile neovasculature, driven primarily by vascular endothelial growth factor, facilitating recurrent microhemorrhage and fibrinolysis perpetuating hematoma expansion. Chronic inflammation sustains disease progression through macrophage polarization, cytokine release, and increased vascular permeability, processes amplified by age-related immune dysregulation and hypoxia-induced factor-1alpha signaling. Impaired tissue repair due to metabolic deficits further limits resolution. Concurrent dysfunction of meningeal lymphatic drainage and fibrotic arachnoid granulations compromises clearance of blood degradation products and inflammatory mediators, while matrix remodeling and cerebrospinal fluid ingress contribute to hematoma persistence. This narrative review presents a pathophysiologic framework highlighting CSDH as a dynamic inflammatory-angiogenic disorder. Pharmacological strategies targeting inflammation, angiogenesis, fibrinolysis, hypoxia, and matrix remodeling hold potential as complements or alternatives to established treatments, including surgical drainage and middle meningeal artery embolization. As the burden of CSDH on healthcare systems rises, translational research and controlled clinical trials will be critical to developing mechanism-driven, multimodal management paradigms. New insights in pathophysiology of chronic subdural hematoma This manuscript fits squarely within the scope of Therapeutic Advances in Neurological Disorders as it provides a comprehensive, mechanistic review of chronic subdural hematoma—a condition projected to become the most common cranial neurosurgical disorder by 2030. By integrating anatomical, molecular, and clinical perspectives, it highlights the pathophysiological processes that underpin disease chronicity and recurrence, while also linking these insights to evolving surgical and adjunctive treatment strategies. The work is directly relevant to neurosurgeons, residents, and students as it addresses both operative considerations and future directions in therapeutic innovation, thereby contributing to the advancement of evidence-based neurosurgical care.