Volume 01 · Issue 02 · 2025

Approximately one-third of the 50 million patients with epilepsy worldwide are resistant to pharmacological treatments and may require aggressive interventions, such as surgery. However, many patients do not benefit from surgery due to anatomical challenges or multifocal epileptogenic origins. Deep brain stimulation (DBS) is a promising alternative for these patients. DBS modulates neurotransmitter activity to prevent seizure propagation and has already been approved for the treatment of Parkinson’s disease and essential tremors. Although the anterior nucleus of the thalamus is the only DBS target approved for drug resistant epilepsy in Europe and Canada, the centromedian nucleus (CM) has emerged as a promising target, particularly for generalized and frontal lobe seizures. The CM is challenging to target because of its small size and complex connections, and it cannot be easily visualized using conventional imaging. This study focused on advanced methods for CM identification, including specialized magnetic resonance imaging sequences, intraoperative neurophysiological recordings, and diffusion tensor imaging tractography. These techniques are crucial for precise DBS targeting and for improving seizure control in affected patients. Our findings indicate that combining these advanced imaging and neurophysiological methods enhances the accuracy of DBS, potentially expanding its therapeutic applications in epilepsy. By optimizing CM-DBS electrode placement, these approaches can improve clinical outcomes in drug resistant epilepsy, making them vital for effective treatment strategies.

Stroke is a leading cause of disability and death, and ischemic stroke accounts for >70% of the stroke incidence. Recanalization (intravenous thrombolysis or endovascular thrombectomy) is the main treatment for ischemic stroke and an effective means of restoring cerebral blood perfusion. However, >50% of patients who undergo recanalization do not achieve the desired outcome. Inflammation-mediated ischemic injury is likely a major contributor to poor patient outcomes following recanalization. The Janus kinase (JAK) pathway, a rapid membrane-nuclear signaling pathway, induces the expression of various key inflammatory mediators. Four JAK family members (JAK1, JAK2, JAK3, and tyrosine kinase 2 [TYK2]) have been identified, of which JAK2 is the family member most often associated with ischemic stroke. This article reviews and summarizes recent studies on the JAK2-mediated inflammatory pathway in patients with ischemia, with an additional emphasis on the potential application of JAK2 inhibitors as a treatment for ischemic injury.

In young individuals, the prevalence of autoimmune encephalitis with antibodies against the N-methyl-D-aspartate receptor (NMDAR) exceeds that of any individual viral cause. Limited reviews on biomarkers of anti-NMDAR encephalitis have been published to date. Here, we review the biomarkers of anti-NMDAR encephalitis, aiming to elucidate the potential mechanisms revealed by biomarkers. This review introduces the concept, clinical characteristics, mechanisms, and diseases associated with anti-NMDAR encephalitis. The second section reviews the biomarkers of anti-NMDAR encephalitis, including the subunits of NMDAR, NMDAR antibody, inflammatory factors, chemokines, micro ribonucleic acids (miRNAs), mitochondrial deoxyribonucleic acid (DNA), neurofilament light chain, clinical index, electroencephalogram, genes, and other biomarkers. The relationship between the factors and anti-NMDAR encephalitis, and the considered evidence levels are also revealed at the end of the review.

In China, acute ischemic stroke (AIS) predominates as the leading form of stroke and stands as a significant contributor to the nation’s stroke burden. A concerning sequel to AIS, early neurological deterioration (END), profoundly influences patient outcomes, often suggesting poor prognoses. Despite extensive research, the precise etiology and pathogenesis of END remain elusive, complicating clinical interventions and accentuating the demand for reliable predictive tools. This review seeks to elucidate the current understanding of and advances in prediction tools for END in AIS, aiming to furnish clinicians with insights for risk stratification and to propel the research endeavours in predictive tool development.

Microglia, which are resident phagocytic cells in the brain, are involved in the active clearance of microbes, misfolded proteins, and cell debris, among others. In Alzheimer’s disease, microglia play a pivotal role in clearing extracellular amyloid-β (Aβ) plaques and intracellular Tau aggregates from the brain. Microglial cells have several mechanisms for Tau internalization, including macropinocytosis, heparan sulfate proteoglycans (HSPGs), dynamin-dependent endocytosis, and receptor-mediated endocytosis. Internalized Tau seeds either undergo proteasomal or lysosomal degradation or are exocytosed into the extracellular space via exosomes. Microtubule-associated protein 1 light chain 3 (LC3)-associated endocytosis (LANDO) is a recently discovered microglial mechanism for an effective clearance of Aβ aggregates and alleviates neurodegeneration in murine Alzheimer’s disease. Several microglial receptors are reported to be involved in misfolded Aβ and Tau aggregate internalization such as triggering receptor expressed on myeloid cell 2 (TREM-2), purinergic receptor P2Y12 (P2Y12R), C-X3-C motif chemokine receptor 1 (CX3CR1), etc.

In this study, we report the LANDO of Tau monomers and aggregates by murine microglial cells, which are further degraded by lysosomal fusion. LANDO of extracellular Tau is demonstrated by several biochemical and cell-biology experiment including Western blotting, fluorescence and confocal imaging of microglial cells.

We analyzed microglial activation by measuring the upregulation of ionized calcium-binding adapter molecule 1 (Iba-1) expression. Later, we demonstrated the LANDO of human full-length Tau species, where LC3 colocalizes with internalized Tau, followed by lysosomal degradation by microglia. The accumulation of internalized Tau in the perinuclear region of the cell in the presence of chloroquine supports phagolysosomal fusion and degradation.

Microglia internalize extracellular Tau species via LANDO, which further undergoes degradation via the lysosomal pathway.

The objective of this study is to assess the severity of amyotrophic lateral sclerosis (ALS) patients by comparing relevant nerve conduction study (NCS) indices between the accessory and limb nerves, with the aim of identifying distinctive electrophysiological markers that precede symptoms, to facilitate the early diagnosis of ALS and guide subsequent follow-up measures.

A total of 54 patients with ALS were enrolled at Renmin Hospital of Wuhan University from 2018 to 2020. Patients were consecutively recruited, and their sex, age, time of referral, presenting symptoms, site of onset, modified ALS functional rating scale-revised (ALSFRS-R) score, and electrophysiological findings were retrospectively recorded and analyzed.

A total of 54 patients with ALS were included, with a male-to-female ratio of 2.38. The ALSFRS-R scores of the 54 ALS patients ranged from 27 to 46, with mean (± standard deviation [SD]) of 39.26 ± 4.63, with no significant gender difference in scores (t = 0.438, P = 0.663). In regards to electrophysiological indices, there were 19, 14, 2, 8, and 18 patients with distal motor latency (DML) prolongation and 36, 29, 7, 16, and 6 patients with decreased compound muscle action potential (CMAP) amplitudes of the median, ulnar, tibial, peroneal, and accessory nerves, respectively. Correlation and regression analysis revealed that ALSFRS-R score was negatively correlated with age (r = -0.337, P = 0.013) and DML of median nerve (r = -0.340, P = 0.012), and positively correlated with the CMAP amplitudes of median (r = 0.549, P <0.001), ulnar (r = 0.438, P = 0.001), tibial (r = 0.428, P = 0.001), peroneal (r = 0.426, P = 0.001), and accessory (r = 0.326, P = 0.016) nerves. The independent influencing factors of the ALSFRS-R score were the CMAP amplitudes of the median nerve (B = 1.023, P = 0.002) and the accessory nerve (B = 0.460, P = 0.0497).

CMAP amplitudes in the median and accessory nerves are closely related to the ALSFRS-R score, which can be used as a crucial observational index to objectively reflect the severity of ALS.

Within the dual stream model for language, the bilateral dorsal superior temporal gyrus (STG) is associated with spectro-temporal analysis while the mid-post superior temporal sulcus is associated with processing of higher-level phonological codes. However, the true lateralization of functions needed for phonological discrimination at the word level remains unsettled. The aim of the present work was to determine if individuals with acute stroke primarily involving the left STG and middle temporal gyrus (MTG) demonstrated poorer discrimination (d’) between phonologically related words in a word-picture verification task than those with left hemisphere lesions outside the temporal lobe and compared to those with right hemisphere stroke. The latter would support a left bias and provide an estimate of the magnitude.

One hundred fourteen individuals with acute stroke completed both acute magnetic resonance imaging and a word-picture verification task with phonological and semantic foils. Eighty-nine participants had left hemisphere stroke (51 included the temporal lobe). Twenty participants had right hemisphere stroke (14 included the temporal lobe). Five participants with bilateral stroke were included (3 included the bilateral temporal lobes). Quantile regression was performed controlling for overall lesion volume, age, and sex.

While more than half of patients performed the task well, patients with left temporal lobe lesions were more likely to perform poorly.

These results confirm a role for the left superior temporal lobe, including the STG, in phonological processing during word recognition, and indicate that a subset of individuals (<50%) have varying degrees of left bias in discrimination of phonologically similar words in the STG.

Submission deadline:31 December 2025