Intrabody B1 targeting TDP-43 modulates neuroinflammatory and metabolic pathways in a preclinical ALS model.

Postoperative delirium (POD) is a common perioperative neurocognitive complication in older adults and is closely associated with adverse outcomes, including progressive cognitive decline, loss of functional independence, and increased healthcare burden. Identifying potentially modifiable drug-related factors is therefore of clear clinical importance (). Dexmedetomidine, a highly selective α2-adrenoceptor agonist, is widely used for intraoperative and procedural sedation and is generally regarded as a relatively delirium-sparing sedative. Recent evidence supports this view. A 2024 meta-analysis of randomized controlled trials in non-cardiac surgery showed that intraoperative intravenous dexmedetomidine was associated with a lower incidence of POD, although bradycardia and hypotension occurred more frequently (). In addition, among older patients undergoing lower-limb orthopedic surgery under spinal anesthesia, dexmedetomidine sedation was associated with a lower rate of POD than propofol sedation (). Nevertheless, dexmedetomidine may not be uniformly protective in all settings, and recent case reports have described paradoxical delirium-like reactions during routine infusion (). Although reserpine is no longer a first-line antihypertensive drug, it is still used in some clinical situations. Existing research suggests that reserpine can alter central monoaminergic signaling by affecting the vesicular storage of monoamine neurotransmitters and may be associated with neuropsychiatric abnormalities (, ). However, relevant modern clinical data are very limited, and existing direct evidence mainly comes from early case reports on withdrawal psychosis or manic-like reactions (, ). To the best of our knowledge, no prior case report has specifically described this clinical scenario; therefore, we report an acute hyperactive delirium-like episode during dexmedetomidine sedation in a patient who had recently discontinued long-term reserpine therapy before surgery. A 63-year-old woman (height 160 cm, weight 55 kg) was scheduled to undergo arthroscopic meniscectomy of the knee. She had a 10-year history of hypertension treated with reserpine (0.1 mg/day), which had been discontinued 7 days before surgery. After discontinuation, her preoperative blood pressure remained relatively stable, ranging from 131/84 to 142/86 mmHg, and no alternative antihypertensive therapy was initiated before surgery. Her medical history was otherwise notable only for an appendectomy 20 years earlier. Preoperatively, cognitive function was normal, with no evidence of anxiety, sleep disturbance, or previous psychiatric illness. Laboratory findings were unremarkable.