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Introduction: Neuroleptic malignant syndrome (NMS), thought to arise through dopamine antagonism, is life-threatening. While prompt diagnosis of NMS is critical, it may be obscured by other diagnoses, such as malignant catatonia, with overlapping, life-threatening symptoms. Initiation of dopamine-blocking agents such as antipsychotics and abrupt cessation of dopaminergic medications such as amantadine can precipitate NMS. Once NMS is suspected, deft medical management should ensue. Multiple case reports detail electroconvulsive therapy's (ECT's) effectiveness in the treatment of NMS. While this relationship is well-documented, there is less literature regarding comparative efficacy of ECT in the acute treatment of NMS-like states precipitated by withdrawal of dopamine agonists, such as amantadine. Case: We present a 52-year-old female with schizoaffective disorder bipolar type, with a history of a lorazepam-resistant catatonic episode the prior year that had responded to amantadine. She presented febrile with altered mental status, lead pipe rigidity, mutism, grasp reflex, stereotypy, autonomic instability, and a Bush-Francis Catatonia Rating Scale (BFCRS) of 24, suggesting malignant catatonia versus NMS. There was concern over a potentially abrupt cessation of her amantadine of which she had been prescribed for the past year. Interventions: Organic etiologies were ruled out, and a presumptive diagnosis of NMS was made with central dopaminergic depletion from abrupt dopamine agonist (amantadine) withdrawal as the suspected underlying etiology. After intravenous lorazepam and reinduction of amantadine failed to alleviate her symptoms, urgent ECT was initiated. Our patient received an index series of ECT of seven treatments. After ECT #1 she was no longer obtunded, after treatment #2 her symptoms of mutism, rigidity, stereotypy, and agitation showed improvement, and by ECT #3, the NMS had rapidly dissipated as evidenced by stable vital signs, lack of rigidity, and coherent conversation. Conclusion: Brisk identification of potentially life-threatening NMS and NMS-like states, including malignant catatonia, warrants a trial of ECT. ECT's theoretical mechanisms of action coincide with the theoretical pathophysiology of the conditions. It is a viable and safe treatment option for reducing mortality. With prompt initiation of ECT, we obtained rapid control of a condition with a potentially high mortality.
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Onset of the mitochondrial permeability transition (MPT) plays a causative role in ischemia/reperfusion (I/R) injury. Current therapeutic strategies for reducing reperfusion injury remain disappointing. Autophagy is a lysosome-mediated, catabolic process that timely eliminates abnormal or damaged cellular constituents and organelles such as dysfunctional mitochondria. I/R induces calcium overloading and calpain activation, leading to degradation of key autophagy-related proteins (Atg). Carbamazepine (CBZ), an FDA-approved anticonvulsant drug, has recently been reported to increase autophagy. We investigated the effects of CBZ on hepatic I/R injury. Hepatocytes and livers from male C57BL/6 mice were subjected to simulated in vitro, as well as in vivo I/R, respectively. Cell death, intracellular calcium, calpain activity, changes in autophagy-related proteins (Atg), autophagic flux, MPT and mitochondrial membrane potential after I/R were analyzed in the presence and absence of 20 µM CBZ. CBZ significantly increased hepatocyte viability after reperfusion. Confocal microscopy revealed that CBZ prevented calcium overloading, the onset of the MPT and mitochondrial depolarization. Immunoblotting and fluorometric analysis showed that CBZ blocked calpain activation, depletion of Atg7 and Beclin-1 and loss of autophagic flux after reperfusion. Intravital multiphoton imaging of anesthetized mice demonstrated that CBZ substantially reversed autophagic defects and mitochondrial dysfunction after I/R in vivo. In conclusion, CBZ prevents calcium overloading and calpain activation, which, in turn, suppresses Atg7 and Beclin-1 depletion, defective autophagy, onset of the MPT and cell death after I/R.