Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) is a new immune checkpoint molecule and its role of primary central nervous system lymphoma (PCNSL) tumor microenvironment has been unclear. We explored the Siglec-15 and programed death-ligand 1 (PD-L1) expression in tumor tissues and analyzed the association between the expression of these molecules and overall survival in newly diagnosed PCNSL. A total of 60 patients diagnosed with diffuse large B-cell lymphoma in PCNSL were included in this study. The Siglec-15 and PD-L1 expression on tumor cells, intratumoral macrophages and peritumoral macrophages were immunohistochemically evaluated. The expression of Siglec-15 and PD-L1 was greater in macrophages than in tumor cells. Regarding peritumoral macrophages, the number of Siglec-15-positive samples (n = 24) was greater than the number of PD-L1-positive samples (n = 16). A multivariate Cox analysis showed that the Siglec-15 positivity of peritumoral macrophages and performance of high-dose methotrexate-based chemotherapy were independent predictors of overall survival (hazard ratio: 0.295 and 0.322, respectively). The Kaplan–Meier survival curves showed that patients with Siglec-15-positive peritumoral macrophages had longer overall survival than those with Siglec-15-negative peritumoral macrophages (median overall survival: 3018 days and 746 days, respectively; p = 0.0290). Our findings indicate that the expression of Siglec-15 on peritumoral macrophages induces a favorable outcome in PCNSL patients.

Transcranial magnetic stimulation (TMS) is commonly employed for diagnostic and therapeutic purposes to enhance recovery following brain injury, such as stroke or intracerebral hemorrhage (ICH). Single-pulse TMS, most commonly used for diagnostic purposes and with motor evoked potential (MEP) recordings, is not suitable for clinical use in patients with severe motor paresis. To overcome this problem, we developed a quadripulse theta burst transcranial magnetic stimulation (QTS) device that combines the output from 16 stimulators to deliver a train of 16 monophasic magnetic pulses through a single coil. High-frequency theta rhythm magnetic bursts (bursts of four monophasic pulses, at 500 Hz, i.e., with a 2-ms interpulse interval, repeated at 5 Hz) were generated via a set of 16 separate magnetic stimulators connected to a specially designed combination module. No adverse effects or electroencephalogram (EEGs) abnormalities were identified during or after the recordings. MEP amplification in the QTS during four-burst theta rhythm stimulations produced four independent MEPs 20 ms after each burst onset maximizing the final third or fourth burst, which exhibited significantly greater amplitude than those resulting from a single burst or pulse. Motor functional palsy grades after ICH and QTS-MEP parameters and resting motor threshold (RMT) and amplitudes were significantly correlated (r = −0.83/−0.81 and 0.89/0.87; R2 = 0.69/0.66 and 0.79/0.76, p < 0.001; anterior/posterior-stimulus polarity, respectively). In conclusion, QTS-MEPs enabled a linear functional evaluation in patients with various degrees of motor paresis. However, the benefits, safety, and limitations of this device should be further explored in future studies.

A stable, reliable, non-invasive, quantitative assessment of swallowing function remains to be established. Transcranial magnetic stimulation (TMS) is commonly used to aid in the diagnosis of dysphagia. Most diagnostic applications involve single-pulse TMS and motor evoked potential (MEP) recordings, the use of which is not clinically suitable in patients with severe dysphagia given the large variability in MEPs measured from the muscles involved in swallowing. Previously, we developed a TMS device that can deliver quadripulse theta-burst stimulation in 16 monophasic magnetic pulses through a single coil, enabling the measurement of MEPs related to hand function. We applied a system for MEP conditioning that relies on a 5 ms interval-monophasic quadripulse magnetic stimulation (QPS5) paradigm to produce 5 ms interval-four sets of four burst trains; quadri-burst stimulation (QBS5), which is expected to induce long-term potentiation (LTP) in the stroke patient motor cortex. Our analysis indicated that QBS5 conditioned left motor cortex induced robust facilitation in the bilateral mylohyoid MEPs. Swallowing dysfunction scores after intracerebral hemorrhage were significantly correlated with QBS5 conditioned-MEP parameters, including resting motor threshold and amplitude. The degree of bilateral mylohyoid MEP facilitation after left side motor cortical QBS5 conditioning and the grade of severity of swallowing dysfunction exhibited a significant linear correlation (r = −0.48/−0.46 and 0.83/0.83; R2 = 0.23/0.21 and 0.68/0.68, P < 0.001; Rt./Lt. side MEP-RMT and amplitudes, respectively). The present results indicate that RMT and amplitude of bilateral mylohyoid-MEPs after left motor cortical QBS5 conditioning as surrogate quantitative biomarkers for swallowing dysfunction after ICH. Thus, the safety and limitations of QBS5 conditioned-MEPs in this population should be further explored.