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Objective: Gamma knife radiosurgery (GKRS) has served as an adjunctive treatment in Cushing’s disease (CD) for decades and has become a vital part of therapy in the management of CD. Biological effective dose (BED) is a radiobiological parameter with time correction, considering the cellular deoxyribonucleic acid repairment. We aimed to investigate the safety and efficacy of GKRS for CD and evaluate the association of BED and treatment outcome. Methods: A cohort study of 31 patients with CD received GKRS in West China Hospital between June 2010 and December 2021. Endocrine remission was defined as normalization of 24 h urinary free cortisol (UFC) or serum cortisol ≤ 50 nmol/L after a 1 mg dexamethasone suppression test. Result: The mean age was 38.6 years old, and females accounted for 77.4%. GKRS was the initial treatment for 21 patients (67.7%), and 32.3% of patients underwent GKRS after surgery due to residual disease and recurrence. The mean endocrine follow-up duration was 22 months. The median marginal dose was 28.0 Gy, and the median BED was 221.5 Gy2.47. Fourteen patients (45.1%) experienced control of hypercortisolism in the absence of pharmacological treatment, and the median duration to remission was 20.0 months. The cumulative rates of endocrine remission at 1, 2, and 3 years after GKRS were 18.9%, 55.3%, and 72.21%, respectively. The total complication rate was 25.8%, and the mean duration from GKRS to hypopituitary was 17.5 months. The new hypopituitary rate at 1, 2, and 3 years were 7.1%, 30.3%, and 48.4%, respectively. A high BED level (BED > 205 Gy2.47) was associated with better endocrine remission than a low BED level (BED ≤ 205 Gy2.47), while no significant differences were found between the BED level and hypopituitarism. Conclusions: GKRS was a second-line therapeutic option for CD with satisfactory safety and efficacy. BED should be considered during GKRS treatment planning, and optimization of BED is a potentially impactful avenue toward improving the efficacy of GKRS.

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Intracerebral hemorrhage (ICH) is a neurological disease with high mortality and disability. Recent studies showed that white matter injury (WMI) plays an important role in motor dysfunction after ICH. WMI includes WMI proximal to the lesion and WMI distal to the lesion, such as corticospinal tract injury located at the cervical enlargement of the spinal cord after ICH. Previous studies have tended to focus only on gray matter (GM) injury after ICH, and fewer studies have paid attention to WMI, which may be one of the reasons for the poor outcome of previous drug treatments. Microglia and astrocyte-mediated neuroinflammation are significant mechanisms responsible for secondary WMI following ICH. The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome activation, has been shown to exacerbate neuroinflammation and brain injury after ICH. Moreover, NLRP3 inflammasome is activated in microglia and astrocytes and exerts a vital role in microglia and astrocytes-mediated neuroinflammation. We speculate that NLRP3 inflammasome activation is closely related to the polarization of microglia and astrocytes and that NLRP3 inflammasome activation may exacerbate WMI by polarizing microglia and astrocytes to the pro-inflammatory phenotype after ICH, while NLRP3 inflammasome inhibition may attenuate WMI by polarizing microglia and astrocytes to the anti-inflammatory phenotype following ICH. Therefore, NLRP3 inflammasome may act as leveraged regulatory fulcrums for microglia and astrocytes polarization to modulate WMI and WM repair after ICH. This review summarized the possible mechanisms by which neuroinflammation mediated by NLRP3 inflammasome exacerbates secondary WMI after ICH and discussed the potential therapeutic targets.

Objective: This study evaluated the long-term efficacy of globus pallidus internus (GPi) deep brain stimulation (DBS) in the treatment of Cranio Facial dystonia (Meige syndrome) and investigated the correlation between the volume of tissue activated (VTA) of the GPi and each subregion and movement score improvement.Methods: We retrospectively analyzed the clinical data of 13 patients with drug-refractory Meige syndrome who were treated with GPi DBS. Pre- and postoperative Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores were compared. Relationships between preoperative baseline variables and improvement in the BFMDRS-Movement (BFMDRS-M) score were analyzed. LEAD-DBS software was used for three-dimensional reconstruction of the GPi and implanted electrodes. Correlations between the GPi-VTA and score improvement were analyzed.Results: The average follow-up period was 36.6±11.0 months (18-55 months). The improvements in the BFMDRS-M score were 58.2% and 54.6% at 3 months after stimulation and at the final follow-up visit, respectively, and the improvements in the BFMDRS-Disability (BFMDRS-D) score were 53.6% and 51.7%, respectively. At the final follow-up visit, the improvements in BFMDRS-M scores for the eye, mouth, and speech/swallowing were significant (P<0.001). Age was an independent predictor of improvement in the BFMDRS-M score after DBS (P=0.005). A decrease in the BFMDRS-M score had significant positive relationships with the GPi-VTA (r=0.757, P=0.003). Conclusions: GPi DBS is an effective method to treat drug-refractory Meige syndrome. LEAD-DBS software can be used as an effective aid for visualization programing after DBS.