Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: outcomes of a dedicated anesthesia and surgery protocol.

BACKGROUND: Patients requiring percutaneous endoscopic gastrostomy (PEG) for amyotrophic lateral sclerosis (ALS) related dysphagia represent a clinical challenge. Diminished pulmonary function and aspiration risks can lead to anesthesia-related complications, and gastric displacement from hemidiaphragm elevation may preclude safe gastric access. This study reports the efficacy and outcomes of a dedicated anesthesia/surgery management protocol for ALS patients undergoing PEG. METHODS: In 2013, a PEG placement protocol for ALS patients was developed emphasizing efficient pre-operative evaluation, rapidly metabolized anesthetic agents, and minimization of opioid use. Outcomes were analyzed retrospectively. Preoperative weight loss, pulmonary function tests, total analgesia, procedural time, and 90-day morbidity and mortality were recorded. RESULTS: From 2013-2019, 67 ALS patients (mean age 65.3 years, 52.2% female) received a PEG under the protocol. Mean percentage weight loss 6 months before PEG was 9.3 ± 5.1% with 38.8% of patients meeting criteria for severe malnutrition. Mean anesthesia time (propofol induction to anesthesia emergence) was 34.5 ± 10.8 min and mean operative time (endoscope insertion to dressing placement) was 16.4 ± 8.2 min. Regional anesthesia with liposomal bupivacaine was performed in 76.1%. All attempts at PEG placement were successful. With a mean follow-up of 6.1 ± 6.8 months, all PEGs were functional and there were no surgical site complications. Thirty-day readmission rate was 7.0% and 90-day mortality was 22.4% (46.7% occurring within 30 days). Mean time from surgery to death was 8.8 ± 7.8 months. CONCLUSIONS: Protocols for optimizing PEG may help overcome challenges present in the ALS patient population. Despite patient comorbidities, protocol implementation and dedicated team members resulted in a high procedural success rate and low complication rate. Further study is warranted to optimize the timing of PEG placement in relation to ALS disease progression and determine the utility of regional anesthesia during PEG placement.

Cardiovascular Collapse in a Patient With Parotid Abscess: Dangerous Cross Talk Between the Brain and Heart: A Case Report.

Postsurgical trigeminal neuralgia (TN), although rare, can lead to significant hemodynamic perturbations by triggering the trigeminocardiac reflex (TCR). The combination can lead to diagnostic as well as management challenges for clinicians. We present the case of a patient with a parotid abscess, which developed as a complication of his otolaryngologic surgery, and which led to repeated episodes of symptomatic bradycardia associated with cardiovascular collapse. This case highlights the importance of heightened awareness, early diagnosis, and timely treatment of postsurgical neuropathic pain syndromes to avoid life-threatening complications.

Protein vicinal thiol oxidations in the healthy brain: not so radical links between physiological oxidative stress and neural cell activities.

Reversible oxidations of protein thiols have emerged as alternatives to free radical-mediated oxidative damage with which to consider the impacts of oxidative stress on cellular activities but the scope and pathways of such oxidations in tissues, including the brain, have yet to be fully defined. We report here a characterization of reversible oxidations of glutathione and protein thiols in extracts from rat brains, from two sources, which had been (1) frozen quickly after euthanasia to preserve in vivo redox states and (2) subjected to alkylation upon tissue disruption to trap reduced thiols. Brains were defined, relatively, as Reduced and Moderately Oxidized based on measured ratios of reduced (GSH) to oxidized (GSSG) glutathione. Levels of protein disulfides formed by the cross-linking of closely-spaced (vicinal) protein thiols, but not protein S-glutathionylation, were higher in extracts from the Moderately Oxidized brains compared to the Reduced brains. Moreover, the oxidized vicinal thiol proteome contains proteins that impact cellular energetics, signaling, neurotransmission, and cytoskeletal dynamics among others. These findings argue that kinetically-competent pathways for reversible, two-electron oxidations, of protein vicinal thiols can be activated in healthy brains in response to physiological oxidative stresses. We propose that such oxidations may link oxidative stress to adaptive, but also potentially deleterious, changes in neural cell activities in otherwise healthy brains.

SNAP-25 contains non-acylated thiol pairs that can form intrachain disulfide bonds: possible sites for redox modulation of neurotransmission.

Intrachain disulfide bond formation among the cysteine thiols of SNAP-25, a component of the SNARE protein complex required for neurotransmitter release, has been hypothesized to link oxidative stress and inhibition of synaptic transmission. However, neither the availability in vivo of SNAP-25 thiols, which are known targets of S-palmitoylation, nor the tendency of these thiols to form intrachain disulfide bonds is known. We have examined, in rat brain extracts, both the availability of closely spaced, or vicinal, thiol pairs in SNAP-25 and the propensity of these dithiols toward disulfide bond formation using a method improved by us recently that exploits the high chemoselectivity of phenylarsine oxide (PAO) for vicinal thiols. The results show for the first time that a substantial fraction of soluble and, to a lesser extent, particulate SNAP-25 contain non-acylated PAO-binding thiol pairs and that these thiols in soluble SNAP-25 in particular have a high propensity toward disulfide bond formation. Indeed, disulfide bonds were detected in a small fraction of soluble SNAP-25 even under conditions designed to prevent or greatly limit protein thiol oxidation during experimental procedures. These results provide direct experimental support for the availability, in a subpopulation of SNAP-25, of vicinal thiols that may confer on one or more isoforms of this family of proteins a sensitivity to oxidative stress.