Tapia's Syndrome (Concurrent Unilateral Recurrent Laryngeal and Hypoglossal Nerve Palsy) Following Left Retrosigmoid Craniotomy for Schwannoma Resection.

Tapia's syndrome, a unilateral, extracranial combined lesion to the hypoglossal nerve (cranial nerve [CN] XII) and the recurrent laryngeal branch of the vagal nerve (CN X), has been observed to occur after general anesthesia for a variety of surgical procedures. Surgical intraoperative neck positioning and airway management are hypothesized as causative factors. The condition presents with ipsilateral motor paralysis of the tongue and vocal cords. Postoperatively, patients often present with dysphonia, dysphagia, and difficulty swallowing. We discuss a unique case of Tapia's syndrome occurring after retrosigmoid craniotomy for left vestibular schwannoma resection in a 42-year-old male. General anesthesia was uneventful with an atraumatic, grade 2a intubation and a normal endotracheal tube cuff pressure of 30 cm of water. The patient was positioned laterally, even though the exact head position was not documented. Institutional practice in these cases is for the head to be maintained neutral or with a slight turn. An uneventful subtotal resection of the tumor was performed after retrosigmoid exposure. Postoperatively, the patient complained of left-sided mouth tingling, a hoarse voice, and tongue weakness which impacted his ability to chew and swallow. He had mild left-sided facial weakness and decreased sensation in the V1 and V2 distribution of the trigeminal nerve. Postoperative brain MRI showed postsurgical changes without evidence of neurological or vascular involvement. Fiberoptic endoscopy performed in the otolaryngology clinic showed immobility of the right vocal cord. Consequently, Tapia's syndrome was diagnosed. He later underwent a right vocal fold injection with Prolaryn gel (Merz North America, Inc, Greensboro, NC, USA) via flexible laryngoscopy with a slight improvement in his dysphonia. At his last visit, he declined further interventions based on acceptable voice quality. Tapia's syndrome can occur due to the close anatomical proximity of the hypoglossal and recurrent laryngeal nerves as they pass lateral to the oropharynx and hypopharynx. This predisposes the nerves to anesthetic and surgical insults such as over-stretching of the nerves during head manipulation and trauma to the nerve fibers following laryngoscopy. Our case report highlights this potential rare complication to anesthetic and surgical teams. Awareness of this concurrent paralysis can assist practitioners to rapidly diagnose and treat patients who present in this way postoperatively. It can also enable avoidance of causative factors and remind practitioners of the importance of meticulous perioperative documentation.

CBP/p300 homologs CBP2 and CBP3 play distinct roles in planarian stem cell function.

Chromatin modifications function as critical regulators of gene expression and cellular identity, especially in the regulation and maintenance of the pluripotent state. However, many studies of chromatin modification in stem cells-and pluripotent stem cells in particular-are performed in mammalian stem cell culture, an in vitro condition mimicking a very transient state during mammalian development. Thus, new models for studying pluripotent stem cells in vivo could be helpful for understanding the roles of chromatin modification, for confirming prior in vitro studies, and for exploring evolution of the pluripotent state. The freshwater flatworm, Schmidtea mediterranea, is an excellent model for studying adult pluripotent stem cells, particularly in the context of robust, whole-body regeneration. To identify chromatin modifying and remodeling enzymes critical for planarian regeneration and stem cell maintenance, we took a candidate approach and screened planarian homologs of 25 genes known to regulate chromatin biology in other organisms. Through our study, we identified six genes with novel functions in planarian homeostasis, regeneration, and behavior. Of the list of genes characterized, we identified five planarian homologs of the mammalian CREB-Binding Protein (CBP) and p300 family of histone acetyltransferases, representing an expansion of this family in planarians. We find that two planarian CBP family members are required for planarian survival, with knockdown of Smed-CBP2 and Smed-CBP3 causing distinct defects in stem cell maintenance or function. Loss of CBP2 causes a quick, dramatic loss of stem cells, while knockdown of CBP3 affects stem cells more narrowly, influencing differentiation of several cell types that include neuronal subtypes and cells of the eye. Further, we find that Smed-CBP1 is required for planarian fissioning behavior. We propose that the division of labor among a diversified CBP family in planarians presents an opportunity to dissect specific functions of a broadly important histone acetyltransferase family.

Autophagy and post-ischemic conditioning in retinal ischemia.

Retinal ischemia is a major cause of vision loss and a common underlying mechanism associated with diseases, such as diabetic retinopathy and central retinal artery occlusion. We have previously demonstrated the robust neuroprotection in retina induced by post-conditioning (post-C), a brief period of ischemia, 24 h, following a prolonged and damaging initial ischemia. The mechanisms underlying post-C-mediated retinal protection are largely uncharacterized. We hypothesized that macroautophagy/autophagy is a mediator of post-C-induced neuroprotection. This study employed an in vitro model of oxygen glucose deprivation (OGD) in the retinal R28 neuronal cell line, and an in vivo rat model of retinal ischemic injury. In vivo, there were significant increases in autophagy proteins, MAP1LC3-II/LC3-II, and decreases in SQSTM1/p62 (sequestosome 1) in ischemia/post-C vs. ischemia/sham post-C. Blockade of Atg5 and Atg7 in vivo decreased LC3-II, increased SQSTM1, attenuated the functional protective effect of post-C, and increased histological damage and TUNEL compared to non-silencing siRNA. TUNEL after ischemia in vivo was found in retinal ganglion, amacrine, and photoreceptor cells. Blockade of Atg5 attenuated the post-C neuroprotection by a brief period of OGD in vitro. Moreover, in vitro, post-C attenuated cell death, loss of cellular proliferation, and defective autophagic flux from prolonged OGD. Stimulating autophagy using Tat-Beclin 1 rescued retinal neurons from cell death after OGD. As a whole, our results suggest that autophagy is required for the neuroprotective effect of retinal ischemic post-conditioning and augmentation of autophagy offers promise in the treatment of retinal ischemic injury.Abbreviations: BECN1: Beclin 1, autophagy related; DAPI: 4',6-diamidino-2-phenylindole; DR: diabetic retinopathy; EdU: 5-ethynyl-2'-deoxyuridine; ERG: Electroretinogram; FITC: Fluorescein isothiocyanate; GCL: Ganglion cell layer; GFAP: Glial fibrillary acidic protein; INL: Inner nuclear layer; IPL: Inner plexiform layer; MAP1LC3/LC3: Microtubule-associated protein 1 light chain 3; OGD: Oxygen-glucose deprivation; ONL: Outer nuclear layer; OP: Oscillatory potential; PFA: Paraformaldehyde; PL: Photoreceptor layer; post-C: post-conditioning; RFP: Red fluorescent protein; RGC: Retinal ganglion cell; RPE: Retinal pigment epithelium; RT-PCR: Real-time polymerase chain reaction; SEM: Standard error of the mean; siRNA: Small interfering RNA; SQSTM1: Sequestosome 1; STR: Scotopic threshold response; Tat: Trans-activator of transcription; TUNEL: Terminal deoxynucleotidyl transferase dUTP nick end labeling.

Gene expression in retinal ischemic post-conditioning.

PURPOSE: The pathophysiology of retinal ischemia involves mechanisms including inflammation and apoptosis. Ischemic post-conditioning (Post-C), a brief non-lethal ischemia, induces a long-term ischemic tolerance, but the mechanisms of ischemic post-conditioning in the retina have only been described on a limited basis. Accordingly, we conducted this study to determine the molecular events in retinal ischemic post-conditioning and to identify targets for therapeutic strategies for retinal ischemia. METHODS: To determine global molecular events in ischemic post-conditioning, a comprehensive study of the transcriptome of whole retina was performed. We utilized RNA sequencing (RNA-Seq), a recently developed, deep sequencing technique enabling quantitative gene expression, with low background noise, dynamic detection range, and discovery of novel genes. Rat retina was subjected to ischemia in vivo by elevation of intraocular pressure above systolic blood pressure. At 24 h after ischemia, Post-C or sham Post-C was performed by another, briefer period of ischemia, and 24 h later, retinas were collected and RNA processed. RESULTS: There were 71 significantly affected pathways in post-conditioned/ischemic vs. normals and 43 in sham post conditioned/ischemic vs. normals. Of these, 28 were unique to Post-C and ischemia. Seven biological pathways relevant to ischemic injury, in Post-C as opposed to sham Post-C, were examined in detail. Apoptosis, p53, cell cycle, JAK-STAT, HIF-1, MAPK and PI3K-Akt pathways significantly differed in the number as well as degree of fold change in genes between conditions. CONCLUSION: Post-C is a complex molecular signaling process with a multitude of altered molecular pathways. We identified potential gene candidates in Post-C. Studying the impact of altering expression of these factors may yield insight into new methods for treating or preventing damage from retinal ischemic disorders.