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Background and Objectives Chronic subdural hematoma (CSDH) is a common neurosurgical condition with high recurrence rates post-surgery (5-30%). Although middle meningeal artery (MMA) embolization is emerging as the standard treatment for recurrent CSDH cases, higher costs, procedural risk and technical limitations remain. Medical treatment options are limited. Etizolam is an anxiolytic with anti-inflammatory platelet-activating factor (PAF) receptor antagonist properties. We report our single-institutional retrospective experience with etizolam in primary and recurrent CSDH, including patients with neurological deficits.Methods Retrospective review of CSDH patients treated with etizolam in our outpatient clinic (exclusions: active thrombotic/thromboembolic disease). Dosing started at 1 mg bedtime, titrated to tolerable levels (1-3 mg). Patients underwent clinical monitoring and serial CT scans. We performed systematic review and metaanalysis of pooled data from prior studies investigating etizolam for CSDH.Results 15 patients (median age 68 years, 80% male; mean follow-up 7 months, range 3 months - 4 years) were treated. Presenting symptoms included gait disturbance (40%), memory dysfunction (26%), hemiparesis (20%), and headache (20%). Six had recurrent CSDH post-surgery; nine had primary CSDH. Etizolam dosage was titrated to 1 mg (n=8), 2 mg (n=5), 3 mg (n=2) as tolerated. Duration of treatment was: 6 weeks in 4 patients (27%), 3 months in 6 patients (40%), and >3 months in 5 patients (33%). Complete radiological resolution occurred in 93% patients (14/15); one required surgery. All three bilateral CSDH cases resolved completely. Etizolam showed promise in two small early studies (n=92) by reducing post-surgical recurrence and surgical need in select primary CSDH cases (especially low-density lesions without paresis), but evidence remains low (small, biased, single-center, unreplicated studies).Conclusions In this small retrospective series, etizolam appeared effective as nonsurgical monotherapy for primary and recurrent CSDH, including cases with neurological deficits and mass effect/midline shift (provided sensorium remained normal). This preliminarily extends prior limited evidence on etizolam efficacy beyond mild cases presenting without neurological deficits. Further multi-center investigation is warranted to confirm efficacy, safety, and role relative to MMA embolization or other adjuvants, potentially reducing surgery and its complications in this frail population.Disclosures V. Shenoy: None. S. Shenoy: None. S. Satyanarayana: None.