Takeshi Shimizu

Background: Neuropathic pain (NP) remains difficult to manage because conventional pharmacological therapies often have limited efficacy and intolerable side effects. Noninvasive neuromodulation techniques have emerged as potential alternatives with fewer adverse effects. Meta-analyses of randomized controlled trials suggest that high-frequency repetitive transcranial magnetic stimulation over the primary motor cortex has analgesic effects; however, its efficacy is modest and restricted by the inability to stimulate deeper brain regions. Low-intensity transcranial focused ultrasound stimulation (TUS) is a novel approach that enables precise targeting of deep brain structures and modulation of neural activity. Although promising in preclinical and preliminary human studies, its long-term therapeutic efficacy for NP remains unknown. Objective: This trial aims to explore the therapeutic effects and safety of repeated TUS sessions in patients with NP. Methods: This randomized, participant-blinded, placebo-controlled, 3-arm, parallel-group clinical trial will enroll 39 participants with NP (pain duration ≥3 months; pain intensity ≥4 on the numerical rating scale). Participants will be randomly allocated to one of three groups: (1) TUS targeting the primary motor cortex, (2) TUS targeting the posterior superior insula, or (3) sham stimulation. Each participant will undergo weekly sessions for 8 weeks. The primary outcome is change in weekly average pain intensity scores recorded in a pain diary. Secondary outcomes include additional pain scales, quality of life measures, psychological assessments, quantitative sensory testing, motor cortical excitability, and adverse events. Results: The first participant was enrolled on April 30, 2025, and 20 participants had been enrolled as of February 28, 2026, with enrollment ongoing. The final analysis will be conducted after completion of follow-up and data verification. Conclusions: To our knowledge, this will be the first randomized controlled trial to examine the long-term therapeutic effects of repeated low-intensity TUS for NP. It will provide exploratory proof-of-concept data regarding its clinical efficacy and safety.

BACKGROUND: Holmes tremor (HT) is a symptomatic tremor that develops weeks to years after stroke, traumatic brain injury, or brain tumor and is characterized by low-frequency, high-amplitude movements at rest, during posture, and with intentional movement. It is thought to result from lesions involving the dopaminergic nigrostriatal system, Guillain-Mollaret triangle, or dentato-rubro-thalamic tract. Because HT is often drug resistant, stereotactic procedures targeting the thalamus are considered. While deep brain stimulation for HT shows long-term efficacy, evidence for radiofrequency thalamotomy remains limited. OBSERVATIONS: An 18-year-old right-handed male developed a coarse tremor of the right hand 1 year after a severe traumatic brain injury at age 16. MRI revealed bilateral cerebellar dentate nucleus hemorrhage, diffuse axonal injury in the left thalamus, and multiple contusions. A diagnosis of posttraumatic HT due to right dentate and left thalamic lesions was made, and ventral intermediate nucleus (Vim) thalamotomy was performed because the tremor was refractory to medication. Tremor improvement was maintained for 18 months postoperatively, with marked enhancement of daily activities and an expansion of the ability to handle various daily tasks. LESSONS: This case illustrates that Vim thalamotomy remains a relevant and effective treatment option for HT. https://thejns.org/doi/10.3171/CASE2675

This study explored radiomic features that help identify non-contrast-enhancing tumors (nCET) by analyzing regions where contrast-enhancing tumors (CET) transformed into nCET after Bevacizumab (BEV) treatment. The BEV cohort included 24 recurrent GBM (rGBM) patients treated with BEV, showing reduced contrast-enhancement on gadolinium-enhanced T1-weighted imaging (T1Gd) imaging. The 11C-methionine positron emission tomography (Met-PET) cohort consisted of 24 newly diagnosed GBM (nGBM) patients with available Met-PET data. VOIs were created from T2WI, FLAIR, T1Gd, and Met-PET to analyze nCET and T2/FLAIR lesions. After significant radiomic features were identified, a prediction model for nCET was developed in the BEV cohort and subsequently evaluated in the Met-PET cohort. A total of 37 and 46 significant radiomic features were found in the BEV and Met-PET cohorts, respectively. The key feature, T2WI_whole_GLCMcorrelation_1, was selected for predictive modeling. The model demonstrated high accuracy (AUC = 0.93, p < 0.0001) in the BEV cohort, with sensitivity and specificity of 0.91, while the Met-PET cohort showed moderate accuracy (AUC = 0.74, p = 0.0053). Image reconstruction using these features also effectively visualized nCET in nGBM. These findings suggest that radiomic features in CET regions transforming to nCET after BEV treatment harbors valuable information for identifying nCET in GBM.

Introduction: Neuropathic pain (NP) remains difficult to manage because conventional pharmacological therapies often have limited efficacy and intolerable side effects. Non-invasive neuromodulation techniques have emerged as potential alternatives with fewer adverse effects. Meta-analyses of randomised controlled trials suggest that high-frequency repetitive transcranial magnetic stimulation over the primary motor cortex has analgesic effects; however, its efficacy is modest and restricted by the inability to stimulate deeper brain regions. Low-intensity transcranial focused ultrasound stimulation (TUS) is a novel approach that enables precise targeting of deep brain structures and modulation of neural activity. Although promising in preclinical and preliminary human studies, its long-term therapeutic efficacy for NP remains unknown. This trial aims to evaluate the therapeutic effects and safety of repeated TUS sessions in patients with NP. Methods and analysis: This randomised, participant-blinded, placebo-controlled, three-arm, parallel-group clinical trial will enrol 39 participants with NP (pain duration ≥ 3 months; pain intensity ≥ 4 on the Numerical Rating Scale). Participants will be randomly allocated to one of three groups: (1) TUS targeting the primary motor cortex, (2) TUS targeting the posterior superior insula, or (3) sham stimulation. Each participant will undergo weekly sessions for eight weeks. The primary outcome is change in weekly average pain intensity scores recorded in a pain diary. Secondary outcomes include additional pain scales, quality of life measures, psychological assessments, quantitative sensory testing, motor cortical excitability, and adverse events. Ethics and dissemination: The protocol has been approved by the University of Osaka Clinical Research Review Board. Written informed consent will be obtained from all participants. Findings will be disseminated via scientific presentations and peer-reviewed publications. Trial registration number: jRCTs052240227 STRENGTHS AND LIMITATIONS OF THIS STUDY: ⇒ This is the first randomised, participant-blinded, placebo-controlled clinical trial evaluating the long-term effects of transcranial focused ultrasound stimulation (TUS) for neuropathic pain. ⇒ TUS is a novel, non-invasive technique that can precisely target deep brain areas using a navigation system, offering the potential to modulate brain function. ⇒ The single-blind design (participants only) may introduce a risk of performance bias, as operators cannot be blinded owing to technical constraints. ⇒ The small sample size may limit statistical power to detect subtle between-group differences.

Treatment strategies for unruptured intracranial aneurysms (UIAs) should be carefully considered with reference to rupture and complication rates. It is also important to minimize the length of hospital stay (LOS) and to ensure a high quality of medical care. In this study, we aim to clarify the factors that affect the LOS of patients treated for UIAs using the Inpatient Clinico-Occupational Database of the Rosai Hospital Group (ICOD-R). This was a nationwide-multicenter study based on ICOD-R data from 2000 to 2019. Patients diagnosed with UIAs who were treated with clipping or coiling were included in the study. Multivariate analysis was performed to identify the factors affecting LOS. LOS was also compared between groups classified by surgical procedure or treatment period. We identified 3294 patients on the database who underwent clipping or coiling of UIAs during the study period. Multivariate analysis revealed hospital admission during the early 2000s and the late 2010s, age, and treating institution to be significantly correlated with LOS (p < 0.05). There was a significant difference between the mean LOS of the clipping group (20.3 days) and the coiling group (9.65 days) (p < 0.001). Compared by treatment period, LOS significantly shortened over time. Our results suggest that the type of treatment, time of treatment, patient age, and the treating institution affect postoperative LOS for UIAs. Although coiling was found to lead to a lower average LOS than clipping, treatment selection should take the characteristics of each patient's aneurysm into consideration.

A 54-year-old man with no medical history presented to our hospital with vomiting, left hemiplegia, and seizures. On arrival, he was experiencing generalized tonic-clonic seizures, which required him to be intubated and deeply sedated. Contrast-enhanced computed tomography revealed extensive venous sinus obstruction from the superior sagittal sinus to the bilateral sigmoid sinus and cerebral edema with intracranial hemorrhage. An intracranial pressure (ICP) monitor was immediately placed intracranially, and mechanical thrombectomy (MT) was performed under ICP monitoring. MT was immediately terminated when the venous sinus was partially recanalized enough to decrease the ICP; then, anticoagulation therapy was initiated. Postoperative follow-up angiography revealed that venous sinus obstruction and intracranial venous perfusion improved over time. Although he had intracranial hemorrhage-induced left hemiplegia and sensory deficits, his condition improved with rehabilitation, and the patient was eventually discharged home. The indication criteria and techniques for MT for cerebral venous sinus thrombosis are yet to be established. As in this case, in patients with impaired consciousness due to intracranial hemorrhage or epilepsy, preoperative ICP monitor placement is deemed useful to evaluate venous perfusion during MT and decide the treatment goal.

A 72-year-old man who had undergone a lumboperitoneal shunt for idiopathic normal pressure hydrocephalus was admitted to our emergency department with fever and disturbance of consciousness 8 days after placement. Computed tomography scan showed pneumocephalus and a right-sided temporal porencephalic cyst with a small bone defect in the right petrous bone. Shunt valve pressure was raised from 145 mmH2O to "virtual off" setting. After 2 weeks, follow-up computed tomography showed improvement of pneumocephalus, and the shunt valve pressure was lowered to 215 mmH2O. Since that time, the patient has a good clinical course without recurrence.Tension pneumocephalus following shunt placement for idiopathic normal pressure hydrocephalus is rare and has never been reported in the early postoperative stage after lumboperitoneal shunt, except for the present one. Temporary raising shunt valve pressure is effective in improving the pneumocephalus. Preoperative screening for congenital bone defects by thin-slice computed tomography may be useful for selecting types of shunt valve and determining postoperative pressure setting.