Hypersensitivity reactions to fibrin sealants used in microvascular decompression (MVD) are rare, and delayed eosinophilic meningoencephalitis with progressive brainstem injury has been scarcely reported. We present a case of severe delayed immune-mediated brainstem injury following fibrin-sealant application during MVD for trigeminal neuralgia, with an emphasis on its neurorehabilitation implications. A male patient with long-standing trigeminal neuralgia underwent MVD using a Teflon pledget secured with Beriplast® fibrin sealant. Immediately after surgery, he developed profound quadriplegia (Medical Research Council [MRC] grade 1 in all extremities). Magnetic resonance imaging on postoperative day (POD) 0 revealed ventral medullary and pontine T2/FLAIR hyperintensity without diffusion restriction, consistent with acute vasogenic edema. Despite complete surgical material removal on POD 1, deficits persisted. By POD 8, new diffusion-restricted lesions appeared, indicating secondary cytotoxic injury. Delayed eosinophilia peaked at 21.0% on POD 62, accompanied by a diffuse rash. Comprehensive workup excluded vascular, infectious, autoimmune, and drug-related causes. On transfer to our rehabilitation center (POD 251), motor strength was MRC 3+ in upper and 2- in lower extremities; the patient remained wheelchair-dependent with severe functional limitation and required assistance for all activities of daily living. Markedly prolonged somatosensory evoked potential and motor evoked potential latencies confirmed irreversible corticospinal and sensory pathway disruption, suggesting a potential ceiling for neuroplasticity-driven recovery in this case. Despite one month of structured inpatient neurorehabilitation, no meaningful functional gain was achieved. This case underscores the importance of early immune-mediated injury recognition and highlights the critical role of neurophysiological assessment in prognostication and rehabilitation goal-setting following catastrophic brainstem injury.
The influence of brain frailty on post-stroke aphasia recovery in the acute phase and its interaction with Speech and Language Therapy (SLT) intensity is unclear. We investigated the association between brain frailty components and language outcome and assessed whether brain frailty modifies the dose-dependent treatment effect of SLT. This is a post-hoc analysis of the LEXI multicenter randomized controlled trial, that enrolled patients with acute post-stroke aphasia from 07/2021 to 09/2024. Patients with pre-stroke cognitive impairment or dementia were not eligible for the trial. Participants were randomized to tablet-assisted SLT (Neolexon application) or standard SLT. Brain frailty was retrospectively assessed by outcome-blinded raters on interrater-adjusted baseline non-contrast CT, using cortical and subcortical atrophy, white matter changes (Fazekas score), lacunes, and chronic infarctions to derive a composite brain frailty score (BFS; range 0-3; higher scores indicate higher brain frailty burden). Primary outcome was the 90-days Bielefelder Aphasia Screening Test percentile rank. 56 patients (median age 75 years; 48.2% female) were included. 43 patients (76.8%) had a BFS of 0-1 and 13 (23.2%) of 2-3. Higher BFS were independently associated with worse 90-day language outcome (β -5.3; 95%CI -10.35 to -0.21; p = 0.042), with higher Fazekas scores contributing most (β -4.0; 95%CI -7.6 to -0.5; p = 0.028). Higher SLT dose was associated with improved outcome (β 0.34; 95%CI 0.07 to 0.61; p = 0.016). There was no statistical evidence that brain frailty modified the association between SLT duration and language outcome (pinteraction = 0.507), although the interaction analysis was limited by sample size. Higher white matter disease burden, as a component of brain frailty, was associated with poorer post-stroke language recovery in patients without pre-stroke cognitive impairment or dementia. We found no evidence that brain frailty modified the association between SLT intensity and language outcome, although larger studies are needed to assess effect modification. Routine imaging-based assessment of white matter disease burden may improve prognostic stratification and neurorehabilitation trial design. ClinicalTrials.gov Identifier: NCT04080817; Study Details. Neolexon® Aphasia-App in Acute Aphasia After Stroke. gov. Date of Registration: September 4, 2019).
Brain glucose metabolism measured by [18F]fluorodeoxyglucose (FDG) PET is a marker of residual activity in disorders of consciousness (DoC). Brain amino acid metabolism remains poorly characterized. We examined cross-sectional and longitudinal glucose and methionine uptake and associations with improvement of consciousness. This is a single-center, prospective, observational study. We consecutively enrolled patients older than 15 years admitted to our Rehabilitation Center between 2017 and 2022 with DoC after severe brain injury, who had adequate glucose control. Within this cohort, we performed 1) an exploratory cross-sectional analysis based on PET data from baseline evaluation (mean 20.9 ± 42.1 months after injury) and 2) a prospective longitudinal study. Participants underwent serial Coma Recovery Scale-Revised (CRS-R) assessments and both FDG and [11C]methionine (MET) PET during routine care. The primary outcome was improvement of consciousness, defined as a ≥2-point increase in CRS-R. Associations between metabolic measures and ΔCRS-R were assessed using Spearman correlation with 95% CIs, with exploratory logistic regression and receiver operating characteristic analyses. We included 60 patients in the cross-sectional study and 43 in the longitudinal analysis. In cross-sectional analyses vs 28 non-DoC controls, patients showed reduced whole-brain glucose metabolism (SUVmax mean difference -5.99 [95% CI -7.63 to -4.35]; p < 0.0001) and higher brainstem MET uptake (SUVmean mean difference 0.15 [95% CI 0.01-0.29]; p = 0.03). During the study, 21 (49%) patients demonstrated clinical improvement, with a median 4-point CRS-R increase (mean age 49.6 ± 19.4 years; 33% female; median CRS-R 11 [interquartile range 6-19]). In longitudinal analyses, improvement was associated with increased glucose SUVmax and higher brainstem MET uptake. CRS-R changes correlated with glucose SUVmax (ρ = 0.43 [95% CI 0.15-0.65]; p = 0.004) and brainstem MET SUVmean (ρ = 0.35 [95% CI 0.06-0.59]; p = 0.021). Brainstem MET SUVmean ≥2.28 discriminated improvement (area under the curve 0.686 [95% CI 0.527-0.846]). Increased brainstem MET uptake was associated with improvement of consciousness and may complement FDG-PET findings in DoC, although interpretation is limited by the single-center design, exploratory analyses, and sample size. Japan Registry of Clinical Trials: jrct.mhlw.go.jp; identifier: jRCTs031180091. Registration, January 21, 2019.
Stroke is a leading cause of disability, associated with impaired motor function and brain connectivity. Mental Simulation Practices (MSP), including Motor Imagery, Mirror Therapy and Action Observation Therapy, have been proposed as neurorehabilitation strategies capable of modulating neural networks. This review aimed to clarify the effects of MSP on brain connectivity using fMRI. A PRISMA-based review was conducted and registered in PROSPERO (CRD420251086743). PubMed, Scopus and Web of Science were searched for randomized controlled trials published between 2015 and 2025 evaluating MSP-based rehabilitation versus conventional rehabilitation in stroke patients. Studies were included if they assessed fMRI-based connectivity changes before and after treatment. Meta-analysis was not performed because of heterogeneity in connectivity metrics and neuroimaging methodologies. Risk of bias was assessed using the Cochrane RoB 2 tool, showing low risk or some concerns. Of 467 identified records, 8 randomized controlled trials involving 249 stroke patients met inclusion criteria. Most studies investigated Motor Imagery-based interventions, while two evaluated Mirror Therapy. Across studies, MSPs were consistently associated with upper limb motor improvement compared with conventional rehabilitation alone, accompanied by significant reorganization of brain networks. Neuroimaging findings demonstrated enhanced connectivity within sensorimotor regions, including the primary motor cortex, postcentral gyrus and inferior parietal lobule, together with modulation of corticospinal and interhemispheric pathways. Several studies also reported normalization of maladaptive activation patterns, reduced excessive sensorimotor connectivity and stronger interactions between motor and cognitive networks, changes correlated with clinical motor recovery. Additional reorganization involved attentional, visual and cognitive systems, suggesting network-level neuroplastic adaptations. Mental simulation practices may represent promising adjunctive interventions in standard stroke rehabilitation programs, given their potential role in modulating brain connectivity.
Young patients with traumatic brain injury (TBI) have a better prognosis than the aged, but the underlying mechanisms are not clear. Here, we identified a population of IL-19+ monocytes derived from cranial bone marrow appearing in the brain after TBI. IL-19+ monocytes inhibit the glial hyper-response and promote neurological recovery after TBI through the IL-19/IL-20R axis, which is defective in aged patients. Further studies have proven that CX3CR1 on the IL-19+ monocytes is attracted by CX3CL1 after TBI, infiltrating the brain, and exerting immunoregulatory effects. Notably, intracerebroventricular injection of recombinant CX3CL1 inhibits excessive neuroinflammation and promotes neurological recovery of aged TBI mice by enhancing the output of cranial IL-19+ monocytes to the brain. Our study demonstrates the important involvement of cranial bone marrow in the repair process after TBI and suggests that the characteristic recruitment of cranial bone marrow-derived regulatory myeloid cells may be an effective approach to improve outcomes of aged TBI.
Determining the optimal timing for the initiation of early rehabilitation in pediatric non-traumatic acquired brain injury (ABI) remains challenging, largely because the onset of injury is often difficult to identify, particularly in infancy. We report the case of a 1-year-old boy with non-traumatic ABI of uncertain onset, in whom mobilization was initiated more than 24 hours after an imaging-based diagnosis. Neurorehabilitation, consisting primarily of active practice, was implemented safely, with no adverse events or neurological deterioration during the intervention. This case suggests that imaging-based assessment may serve as an adjunctive objective reference for determining the timing of early rehabilitation in pediatric non-traumatic ABI.
Plain language summaryDetecting the source of abnormal beta oscillations in Parkinson's Disease: evidence from a case of impaired connection between cerebral cortex and basal ganglia.In Parkinson's Disease, a key feature is an exaggerated, oscillatory activity in the brain called the "beta rhythm", which occurs in the circuit, particularly relevant for motor functions, connecting the cortex (the outer brain layer) and the basal ganglia (the deeper structures). Scientists have long debated whether the exact source of this pathological activity was located in the cortex or in the basal ganglia. This report describes a critical clue from an unexpected event: a person with Parkinson's disease developed temporary swelling (edema) that affected both the sensorimotor cortex and the basal ganglia. Notably, this event was limited to one side of the brain and occurred in a subject who carried a medical device that enables recordings of the beta rhythm from inside the basal ganglia. In this peculiar case, the excessive beta rhythm on the affected side was completely suppressed and only returned once the swelling in the overlying sensorimotor cortex had resolved, even though the edema in the basal ganglia itself had recovered earlier. This unique observation suggests that the integrity of the cortex is essential for the pathological beta rhythm to occur in Parkinson's Disease, lending strong support to the theory that this disruptive electrical rhythm is generated in the cortex before spreading to deeper brain structures such as the basal ganglia. Detecting the source of abnormal beta oscillations in Parkinson's Disease: evidence from a case of impaired connection between cerebral cortex and basal ganglia.In Parkinson's Disease, a key feature is an exaggerated, oscillatory activity in the brain called the “beta rhythm”, which occurs in the circuit, particularly relevant for motor functions, connecting the cortex (the outer brain layer) and the basal ganglia (the deeper structures). Scientists have long debated whether the exact source of this pathological activity was located in the cortex or in the basal ganglia. This report describes a critical clue from an unexpected event: a person with Parkinson's disease developed temporary swelling (edema) that affected both the sensorimotor cortex and the basal ganglia. Notably, this event was limited to one side of the brain and occurred in a subject who carried a medical device that enables recordings of the beta rhythm from inside the basal ganglia. In this peculiar case, the excessive beta rhythm on the affected side was completely suppressed and only returned once the swelling in the overlying sensorimotor cortex had resolved, even though the edema in the basal ganglia itself had recovered earlier. This unique observation suggests that the integrity of the cortex is essential for the pathological beta rhythm to occur in Parkinson's Disease, lending strong support to the theory that this disruptive electrical rhythm is generated in the cortex before spreading to deeper brain structures such as the basal ganglia.
Following brain injury, neuromotor disorders of the upper limb are a major cause of functional disability and poor quality of life. In association with paresis and muscle changes, spasticity leads to motor imbalances responsible for joint deformities in general and in the shoulder in particular. In this expert narrative review, we address the assessment and management of spastic shoulder in patients with brain injury, including analysis of the discomfort and the clinical examination. Motor blocks and electromyography are essential, complementary tools. The definition of personalized SMART objectives (specific, measurable, achievable, realistic, and timely) is a crucial step in treatment planning. Depending on the type of impairment, the severity and the objectives, the treatment will combine conservative approaches (rehabilitation, splints, botulinum toxin injections, and stretching) and targeted surgical procedures (tenotomies, muscle and tendon lengthening, and neurectomies).
Electroencephalography (EEG) based brain-computer interface (BCI) systems require optimal channel selection to achieve high signal quality, reduced setup complexity, and robust usability. This study introduces a comprehensive signal-processing framework to improve the efficiency and accuracy of EEG-driven BCIs. Signal pre-processing incorporates standard EEG denoising techniques, including notch filtering, independent component analysis (ICA), and segmentation into temporal windows to mitigate artifacts and enhance data quality. The channel selection phase employs the novel mothcray optimization (MCO) algorithm, a hybrid approach that integrates moth flame optimization and crayfish optimization to identify the most informative channels. Feature extraction encompasses time-domain statistics, frequency-domain attributes, and connectivity measures, enabling a rich representation of underlying neural dynamics. Classification is performed using an advanced deep neural network architecture tailored for the spatial-temporal characteristics of EEG data. Validated on the BCI competition IV dataset IIa, the proposed model achieves an accuracy rate of 93.92%, outperforming established methods and underscoring its effectiveness. The proposed MCO-based channel selection, multi-domain feature fusion, and enhanced EEGNet classifier demonstrate a significant step forward for practical BCI deployment that requires fast setup, robust operation, and efficient use of resources. It is especially advantageous in applications that rely on a reduced number of EEG channels to enable more comfortable and portable headsets, must sustain stable performance under varying recording conditions in home- or clinic-based neurorehabilitation and assistive communication settings.
Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy linked to repetitive head trauma and definitively diagnosed postmortem. Its proposed clinical correlate in living patients is traumatic encephalopathy syndrome (TES). Within this spectrum, diffuse axonal injury (DAI) and post-traumatic hydrocephalus (PTH) represent interacting mechanisms contributing to long-term neurocognitive decline after traumatic brain injury (TBI). While DAI reflects largely irreversible axonal damage, PTH constitutes a potentially reversible disturbance of cerebrospinal fluid (CSF) dynamics. Their coexistence and pathophysiological interplay remain underrecognized. Understanding this continuum is essential to guide therapeutic strategies targeting both structural injury and CSF circulation abnormalities. A narrative review of PubMed-indexed literature (1980-2025) was conducted, focusing on pathophysiological correlations, neuroimaging features, and management strategies for CTE/TES, DAI, and PTH. Case series, clinical trials, and review articles addressing post-traumatic CSF disturbances were prioritized. A total of 100 records were identified (85 via database search, 15 through citation tracking). After screening, 32 were excluded, and 62 articles were included following full-text review. No duplicates were identified. Studies not relevant to pathophysiology, diagnosis, or management were excluded. Persistent ventriculomegaly after TBI is frequently misinterpreted as cerebral atrophy rather than hydrocephalus, leading to missed opportunities for surgical intervention. Advanced neuroimaging improves differentiation between DAI-related atrophy and treatable PTH. Selected patients demonstrate meaningful functional recovery following CSF diversion procedures, including programmable shunts and endoscopic third ventriculostomy. This continuum highlights the importance of recognizing reversible components of post-traumatic injury. Early identification and appropriate management of PTH may significantly improve functional outcomes in patients with chronic TBI.
Emerging evidence suggests that amyotrophic lateral sclerosis (ALS) mortality is elevated following traumatic brain injury (TBI), reflecting a consequence of potential prodromal ALS, though the temporal patterns and underlying mechanisms remain unclear. We aimed to evaluate ALS mortality among individuals with TBI and examine temporal patterns. This study leveraged a retrospective cohort study of 20,250 individuals with complicated mild-to-severe TBI enrolled in the TBI Model Systems (TBIMS) from 1987 to 2024, with a cumulative 198,662 person-years (mean [standard deviation] = 9.8 [7.1] years) of follow-up. Standardized mortality ratios (SMRs) were calculated using the National Institute for Occupational Safety and Health Life Table Analysis System R package, adjusting for age, sex, race, and calendar year. Secondary analyses evaluated temporal patterns and injury severity differences in ALS mortality. Among 4,313 decedents in TBIMS, 11 died of ALS, representing significantly elevated mortality from ALS (SMR = 2.39; 95% confidence interval [CI]: 1.19-4.27) compared with the general population. Time-stratified analyses showed elevated ALS mortality within 2 years post-injury (SMR = 4.30; 95% CI: 1.17-11.01), but not after 2 years (SMR = 1.90; 95% CI: 0.76-3.92). Elevated ALS mortality was also observed within 2 years post-injury among those with severe TBI (SMR = 5.00; 95% CI: 1.03-14.61) and when including individuals with ALS at admission (SMR = 6.45; 95% CI: 2.37-14.04). ALS mortality was higher in the TBIMS cohort than in the general population, and this association was confined to within 2 years of injury. This pattern suggests potential reverse causality, whereby some TBIs in the cohort may have occurred in the setting of prodromal or pre-symptomatic ALS. Further investigation into TBI as a sign of subclinical ALS is warranted.
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Matching brain stimulation to the brain's natural rhythms can drive plasticity, yet this principle has rarely been tested in humans. We targeted the cerebellum, a key hub for motor coordination and learning, using a rhythm-tuned protocol that pairs theta-frequency transcranial alternating current stimulation with intermittent theta-burst stimulation to engage plasticity of cerebello-cortical circuits. In young healthy adults, this pairing enhanced fine motor control and hand dexterity, with gains closely tracking physiological markers of cerebellar-driven plasticity. Applying the same approach in chronic stroke survivors yielded parallel behavioral and neural gains, demonstrating preserved rhythm-plasticity coupling despite injury. Control experiments confirmed both frequency specificity and site specificity, underscoring the mechanistic precision of the intervention. By linking theta-frequency cerebellar stimulation to circuit-level and functional outcomes, these findings establish a biologically grounded framework for targeted neurorehabilitation. Rhythm-specific cerebellar stimulation provides a scalable strategy for enhancing plasticity and improving motor function across movement disorders and motor impairments.
Ischemic stroke (IS) prognosis is frequently compromised by secondary systemic and neuropsychiatric complications extending beyond the initial brain injury. The hypothalamic-pituitary-adrenal (HPA) axis, the primary neuroendocrine regulator, plays a pivotal yet underappreciated role in the pathogenesis of these sequelae. This review analyzes the adverse impact of HPA axis dysregulation on post-stroke outcomes across disease phases. In the acute phase, maladaptive glucocorticoid surges and circadian disruption drive metabolic disturbances, blood-brain barrier (BBB) breakdown leading to hemorrhagic transformation, and stroke-induced immunodepression that predisposes patients to pneumonia. In the chronic phase, persistent HPA hyperactivity, driven by impaired negative feedback and glucocorticoid receptors (GRs) resistance, induces structural remodeling in emotional and cognitive circuits. This serves as a shared pathophysiological mechanism underpinning post-stroke depression, anxiety, and cognitive impairment. Consequently, elucidating these neuroendocrine-immune interactions provides a novel pathophysiological framework for understanding post-stroke multidimensional complications.
Prior studies have linked the microbiota to brain diseases, whereas the longitudinal effects of the oral microbiota on cortical thinning and cognitive impairments in cerebral small vessel disease (CSVD) remain unexplored. We recruited 120 CSVD patients and 40 healthy controls (HCs). The subgingival plaque microbiota was sequenced by a metagenomic approach. Cortical thickness was assessed using GM-centile, an age- and sex-normalized MRI metric. Differential microbial taxa and KEGG orthologs (KOs) between groups were identified using MaAsLin2. Associations between key differential taxa with CSVD-specific cortical thinning were examined using the Spearman test, and those with MoCA score and plasma inflammatory markers (CRP and lymphocyte counts) were examined by linear regression models. Mediation models evaluated the indirect role of cortical thinning in the relationship between microbial abundance and cognitive function. Generalized estimation equations validated the longitudinal effects of the microbiota on cortical thinning progression. We identified distinct oral microbiota dysbiosis in CSVD, including depletion of g_Selenomonas and g_Leptotrichia and enrichment of g_Treponema. The abundance of these microbes was correlated with longitudinal cortical thinning in the frontal gyrus, insular lobes, and inferotemporal gyrus. Enrichment analysis revealed that CSVD-enriched KOs were linked to the upregulation of LPS-mediated pro-inflammatory pathways, while those depleted were associated with the reduced biosynthesis of neuroprotective short-chain fatty acids (SCFAs). g_Leptotrichia abundance showed negatively correlation with CRP (p = 0.045). Mediation analyses indicated that the association between g_Leptotrichia depletion and baseline cognitive impairment was mediated by bilateral insular cortical thinning (both p < 0.05). Additionally, the association between g_Leptotrichia depletion and one-year cognitive decline was mediated by superior frontal cortical thinning (p = 0.033). Oral microbiota dysbiosis in CSVD patients reflects a pro-inflammatory state, characterized by enhanced LPS synthesis and reduced SCFAs production. This dysbiosis is associated with CSVD-specific cortical thinning in regions vulnerable to neuroinflammation, which in turn mediates cognitive impairment. A major strength of this study is the use of population-based, age-, and sex-normalized cortical thickness measurements to quantify cortical thinning, combined with MaAsLin2 modeling to identify CSVD-associated oral microbiota features. This integrated approach minimizes confounding and enhances the reliability of associations between the oral microbiota and cortical thinning.CSVD patients exhibited distinct oral microbiota dysbiosis characterized by depletion of Selenomonas and Leptotrichia and enrichment of Treponema. KEGG enrichment analysis and plasma inflammatory markers further revealed that this dysbiosis reflects a functional shift toward a pro-inflammatory state, driven by enhanced lipopolysaccharide (LPS) synthesis and dysregulated short-chain fatty acid (SCFA) metabolism.Oral microbiota dysbiosis may accelerate cortical thinning in brain regions vulnerable to CSVD pathology through inflammatory mechanisms, thereby mediating the link between microbial alterations and cognitive outcomes. Specifically, Leptotrichia depletion is associated with baseline cognitive impairment via bilateral insular thinning and with one-year cognitive decline via superior frontal thinning.
FLNA encodes filamin A, a cytoskeletal actin-binding protein with critical roles in neuronal migration, mechano-transduction, and organ morphogenesis. Pathogenic FLNA variants are classically associated with periventricular nodular heterotopia (PVNH), epilepsy, and multisystem manifestations, although interpretation of missense variants remains challenging because of marked variable expressivity and limited functional evidence. We describe a mother-daughter pair carrying the heterozygous FLNA missense variant c.5776 C > T (p.Pro1926Ser). Clinical, electroencephalographic, neuroradiological, cardiological, and genetic data were retrospectively reviewed. Variant interpretation was performed according to ACMG/AMP criteria and supported by in silico and structural analyses. The proband, a 13-year-old girl, presented with migraine with aura, epilepsy responsive to levetiracetam, normal brain MRI, and QT interval prolongation, with no pathogenic variants identified in established long-QT genes. Her mother, who carried the same variant, had focal epilepsy, migraine with aura, and subtle PVNH on brain MRI. Additional family history included a maternally related male cousin reportedly hemizygous for the same variant and affected by a severe congenital multisystem phenotype including valvular and extracerebral abnormalities, overall consistent with FLNA-related disease. The p.Pro1926Ser substitution was absent from population databases, involved a highly conserved residue within immunoglobulin-like repeat 17 of the rod-2 domain, and was predicted to be deleterious by most computational tools. These findings support a likely contributory role of FLNA p.Pro1926Ser in a variably expressive neurodevelopmental and multisystem disorder in which epilepsy represents the predominant neurological phenotype.
Rare neurological syndromes have been reported following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, although a causal relationship remains uncertain. We report the case of a 62-year-old woman who developed progressive neurological impairment temporally associated with BNT162b2 (Pfizer-BioNTech) COVID-19 vaccination, resulting in wheelchair dependence. Brain magnetic resonance imaging (MRI) demonstrated multiple periventricular T2-weighted/fluid-attenuated inversion recovery (T2/FLAIR) hyperintense lesions, including lesions oriented perpendicular to the lateral ventricles, consistent with demyelinating features. A multimodal therapeutic approach was implemented, including gut-directed therapy, intravenous gold-induced cytokine (GOLDIC®) therapy, hyperbaric oxygen therapy (HBOT), intranasal exosome therapy, and structured neurorehabilitation. Over the course of treatment, the patient showed substantial clinical improvement, including recovery of ambulation and functional neurological status. While this case highlights the potential for significant neurological involvement following SARS-CoV-2 vaccination and the possibility of recovery with a multimodal therapeutic approach, the contribution of the individual therapies cannot be determined. Further research is needed to better understand the underlying mechanisms and to evaluate emerging therapeutic strategies, including GOLDIC, in this setting.
Ischemic stroke accounts for 87% of all stroke cases, and remains a leading cause of mortality and disability worldwide. Current reperfusion therapies are limited by narrow therapeutic windows, and cerebral ischemia-reperfusion injury (CIRI) remains a major clinical challenge. Ferroptosis, an iron-dependent form of regulated cell death characterized by lethal lipid peroxidation, has been identified as a key pathological driver of CIRI. Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has shown neuroprotective effects in ischemic stroke, but its underlying mechanism, especially the regulatory effect on ferroptosis via the TAK1-CREB1 signaling axis, remains unclear. To investigate the neuroprotective effect of DHA in ischemic stroke and its molecular mechanism related to the TAK1-CREB1 signaling pathway and ferroptosis regulation. Wild-type (WT) C57BL/6 J mice and astrocyte-specific CREB1 conditional knockout (CREB1 CKO) mice were used to establish a photothrombotic stroke (PTs) model. Neurological function was evaluated by modified neurological severity score (mNSS), Bederson score, Garcia scale and hanging test. Cerebral infarct volume was measured by TTC staining. Cerebral blood flow (CBF) was detected by laser speckle contrast imaging. Histopathological changes were observed by HE and Nissl staining. Mitochondrial ultrastructure was examined by transmission electron microscopy (TEM). The levels of malondialdehyde (MDA), glutathione (GSH), NADPH/NADP+ ratio, ferrous iron (Fe2+) and total iron in brain tissue were detected by biochemical kits. The expression of ferroptosis-related proteins and CREB1 was detected by Western blot and immunofluorescence staining. DHA treatment dose-dependently improved neurological function, reduced infarct volume, restored CBF, and ameliorated histopathological damage in PTs mice. TEM revealed that DHA reversed ferroptosis-typical mitochondrial changes in ischemic brain tissue. Biochemically, DHA decreased MDA, Fe²⁺, and total iron, while increasing GSH and NADPH/NADP⁺ ratio. Mechanistically, DHA dose-dependently upregulated GPX4, xCT, and FTH1, and downregulated ACSL4. Notably, astrocyte-specific CREB1 knockout nearly completely abolished DHA's neuroprotective and anti-ferroptosis effects. DHA promotes neurological rehabilitation after ischemic stroke by targeting the astrocytic TAK1-CREB1 signaling pathway to inhibit ferroptosis. This study provides a novel theoretical basis and promising candidate drug for the clinical treatment of ischemic stroke.
Motor imagery-based brain-computer interface (MI-BCI) applications in stroke rehabilitation aim to match brain activity with real-time feedback, thereby establishing closed-loop neural pathways and providing a basis for evaluating patients' neuroplasticity changes. Thus, constructing EEG datasets under MI paradigms is crucial for optimizing MI-BCI systems and understanding the neural rehabilitation process. However, the current limitations of single MI paradigms and the lack of relevant EEG datasets may restrict the accurate interpretation and effective application in stroke rehabilitation. This study collected EEG data from 24 stroke patients during MI tasks, including a novel "sixth finger" MI and an affected-hand MI paradigm. The dataset comprehensively covers the complete longitudinal stages of stroke rehabilitation: pre-training, post-training, and follow-up periods. The data materials include: (1) raw EEG data, (2) preprocessed data, and (3) patient clinical information. Preliminary analysis using classical machine learning algorithms (CSP + SVM and CSP + LDA) demonstrated an average classification accuracy between the two MI paradigms maintained at approximately 85%~86%. We anticipate that this dataset will facilitate research on MI-BCI paradigms and neuroplasticity for stroke, and contribute to the development of high-efficiency MI-BCI systems in the field of stroke rehabilitation.
Acute disseminated encephalomyelitis (ADEM) is a rare, immune-mediated demyelinating disorder of the central nervous system that typically follows viral or bacterial infections. There are only two known case reports that describe an association with ADEM post rickettsial infection. A female in her 80s presented with progressive neurological decline, including dysarthria, dysphagia and hemiparesis, following recent treatment in Hong Kong for rickettsial infection. Initial CT brain imaging showed a right subcortical infarct. She deteriorated with encephalopathy and respiratory failure, requiring intubation. MRI revealed extensive brain and spinal demyelination. Infectious, autoimmune and paraneoplastic investigations were negative, while serology revealed markedly elevated spotted fever group antibodies. Treatment with high-dose corticosteroids and plasma exchange therapy resulted in significant neurological recovery. She was discharged after rehabilitation with a good recovery at 70%-80% of pre-morbid function. This case supports a possible post-infectious immune-mediated mechanism linking rickettsia and ADEM and underscores the importance of early recognition and treatment of ADEM.