EphrinB2 knockdown in cervical spinal cord preserves diaphragm innervation in a mutant SOD1 mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1G93A mice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via viral-mediated shRNA delivery reduced motor neuron loss and preserved respiratory function by maintaining phrenic motor neuron innervation of diaphragm. EphrinB2 expression was also elevated in human ALS spinal cord. These findings implicate ephrinB2 upregulation as both a transcellular signaling mechanism in mutant SOD1-associated ALS and a promising therapeutic target.

EphrinB2 knockdown in cervical spinal cord preserves diaphragm innervation in a mutant SOD1 mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1-G93A mice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via viral-mediated shRNA delivery reduced motor neuron loss and preserved respiratory function by maintaining phrenic motor neuron innervation of diaphragm. EphrinB2 expression was also elevated in human ALS spinal cord. These findings implicate ephrinB2 upregulation as both a transcellular signaling mechanism in mutant SOD1-associated ALS and a promising therapeutic target.

Nanoscale rules governing the organization of glutamate receptors in spine synapses are subunit specific.

Heterotetrameric glutamate receptors are essential for the development, function, and plasticity of spine synapses but how they are organized to achieve this is not known. Here we show that the nanoscale organization of glutamate receptors containing specific subunits define distinct subsynaptic features. Glutamate receptors containing GluA2 or GluN1 subunits establish nanomodular elements precisely positioned relative to Synaptotagmin-1 positive presynaptic release sites that scale with spine size. Glutamate receptors containing GluA1 or GluN2B specify features that exhibit flexibility: GluA1-subunit containing AMPARs are found in larger spines, while GluN2B-subunit containing NMDARs are enriched in the smallest spines with neither following a strict modular organization. Given that the precise positioning of distinct classes of glutamate receptors is linked to diverse events including cell death and synaptic plasticity, this unexpectedly robust synaptic nanoarchitecture provides a resilient system, where nanopositioned glutamate receptor heterotetramers define specific subsynaptic regions of individual spine synapses.

Weighing in on heart failure: the potential impact of bariatric surgery.

Obesity is a growing worldwide epidemic with significant economic burden that carries with it impacts on every physiologic system including the cardiovascular system. Specifically, the risk of heart failure has been shown to increase dramatically in obese individuals. The purpose of this review is to provide background on the individual burdens of heart failure and obesity, followed by exploring proposed physiologic mechanisms that interconnect these conditions, and furthermore introduce treatment strategies for weight loss focusing on bariatric surgery. Review of the existing literature on patients with obesity and heart failure who have undergone bariatric surgery is presented, compared, and contrasted.

Outcomes of Septal Perforation Repair With Concurrent Endoscopic Sinus Surgery.

OBJECTIVE: This study reviews a cohort of patients in whom septal perforation repair was performed concurrently with endoscopic sinus surgery. We present an endonasal perforation repair technique using bilateral mucosal flaps with an autogenous interposition graft. Intraoperative and postoperative management of the combined surgical patient is discussed and perforation closure outcomes are reported. STUDY DESIGN: Case series. SETTING: Tertiary care center. METHODS: In this institutional review board-approved retrospective chart review, adult patients who underwent concurrent bilateral mucosal flap septal perforation repair and endoscopic sinus surgery from March 1992 to March 2020 were identified. Data on demographics, clinical presentations, perforation size, surgical techniques, and outcomes were extracted and analyzed for patients with a minimum of 3 months of follow-up. RESULTS: Fifty-six patients met study inclusion criteria. Nasal obstruction/congestion was the most frequent symptom reported (80.4%), followed by crusting and epistaxis. Mean perforation size measured at the time of surgery was 14.7 (range, 3-41) mm in length by 9.3 (range, 2-23) mm in height. Temporalis fascia was the most frequent (57.9%) interposition graft material used. Complete perforation closure at the time of the last follow-up was noted in 51 (91.1%) patients. Only 1 failure was noted in the last 48 attempted repairs. CONCLUSION: Patients with a perforated septum may have coexistent chronic sinusitis. The feasibility of attempting concurrent sinus surgery and perforation repair has been questioned. Our review demonstrates a high perforation closure rate when a bilateral mucosal flap procedure is performed after sinus surgery is performed at the same setting.

Fixed Positioning for Decompressive Hemicraniectomy Provides a Larger Diameter Flap than Nonfixed Positioning: A Single-Institution Experience.

BACKGROUND: Decompressive hemicraniectomy (DHC) is well established as an effective life-saving intervention. Although literature documents a correlation between mortality and hemicraniectomy flap size, no literature exists demonstrating whether a larger flap may be achieved with 3-pin fixation devices versus nonfixed positioning (e.g., occipital headrest, gel donut). Therefore, positioning for DHC remains the preference of the institution and attending physician. METHODS: Patients undergoing DHC during 2005-2016 were identified using Current Procedural Terminology codes. Inclusion criteria were: operative note available in the electronic medical record and postoperative head computed tomography (hCT). Exclusion criteria were: age <18 years, missing data in electronic medical record, no postoperative hCT performed, and craniectomy not done with intention of performing a hemicraniectomy (i.e., craniotomy converted to craniectomy). Anteroposterior diameter of the hemicraniectomy flap was measured in millimeters on the postoperative hCT. The average diameter was compared between the fixed positioning and nonfixed positioning groups. RESULTS: Analysis included 522 patients who met inclusion criteria; 363 were in the fixed positioning group, and 159 were in the nonfixed positioning group. The average hemicraniectomy diameter was 132.17 mm in the fixed positioning group, and 129.74 mm in the nonfixed positioning group, which was statistically significant (P = 0.027). CONCLUSIONS: This is the first large-scale single-institution study evaluating whether operative positioning for DHC affects the size of a hemicraniectomy flap. Positioning in 3-point fixation led to a statistically significant larger average diameter compared with nonfixed positioning. This indicates that the risks associated with pin fixation as well as additional time spent in positioning in this fashion are offset by the ability to obtain a larger hemicraniectomy flap, which is associated with decreased mortality.

Gene therapy conversion of striatal astrocytes into GABAergic neurons in mouse models of Huntington's disease.

Huntington's disease (HD) is caused by Huntingtin (Htt) gene mutation resulting in the loss of striatal GABAergic neurons and motor functional deficits. We report here an in vivo cell conversion technology to reprogram striatal astrocytes into GABAergic neurons in both R6/2 and YAC128 HD mouse models through AAV-mediated ectopic expression of NeuroD1 and Dlx2 transcription factors. We found that the astrocyte-to-neuron (AtN) conversion rate reached 80% in the striatum and >50% of the converted neurons were DARPP32+ medium spiny neurons. The striatal astrocyte-converted neurons showed action potentials and synaptic events, and projected their axons to the targeted globus pallidus and substantia nigra in a time-dependent manner. Behavioral analyses found that NeuroD1 and Dlx2-treated R6/2 mice showed a significant extension of life span and improvement of motor functions. This study demonstrates that in vivo AtN conversion may be a disease-modifying gene therapy to treat HD and other neurodegenerative disorders.

Tongue Tied after Shoulder Surgery: A Case Series and Literature Review.

This article presents three cases of cranial nerve palsy following shoulder surgery with general anesthesia in the beach chair position. All patients underwent preoperative ultrasound-guided interscalene nerve block. Two cases of postoperative hypoglossal and one case of combined hypoglossal and recurrent laryngeal nerve palsies (Tapia's syndrome) were identified. Through this case series, we provide a literature review identifying postoperative cranial nerve palsies in addition to the discussion of possible etiologies. We suggest that intraoperative patient positioning and/or airway instrumentation is most likely causative. We conclude that the beach chair position is a risk factor for postoperative hypoglossal nerve palsy and Tapia's syndrome.

The effects of perceived social norms on handwashing behaviour in students.

Handwashing is widely considered the most effective method of preventing the spread of infectious illness. Exploring the determinants of handwashing is vital to the development of interventions to increase this behaviour. A survey based on Social Norms Theory assessed handwashing frequency and perceptions of peer handwashing in 255 university students. Participants reported their own handwashing frequency, and how often they thought their peers washed their hands in particular circumstances, to determine whether misperceptions around handwashing exist, and whether these influence the behaviour of individuals. Gender was found to be a significant determinant of handwashing frequency as females reported washing their hands significantly more often than males. Participants also believed they washed their hands significantly more frequently than their peers. Perceived peer handwashing frequency was significantly correlated with participants' own behaviour. This effect was seen in overall handwashing and in food, waste and illness-related hand washing. These results suggest perceived social norms around hand washing have a clear association with individual behaviour. Future research might test the effectiveness of a social norms intervention in other settings which carry an increased risk of infection spread.

Contemporary applications of frontal sinus trephination: A systematic review of the literature.

Our objective was to perform a systematic review of the literature on contemporary indications and outcomes for frontal sinus trephination and present an illustrative case of an endoscopically assisted repair of a subcutaneous frontal sinus fistula by trephination technique. PubMed and Ovid databases were used as data sources. A systematic review of the English literature was completed to review reports of frontal trephination from 1980 to 2014. Articles meeting inclusion criteria for inflammatory and noninflammatory indications were reviewed. Articles were systematically reviewed and graded by evidence-based medicine level. An illustrative case from our institution is then presented. The systematic review identified 2,621 published studies. Thirty-eight studies were identified for inclusion. The indications, techniques, outcomes, safety, and complications were reviewed for noninflammatory and inflammatory conditions. There were 32 retrospective case series, reports, or cohort studies (level 4), four systematic reviews (level 3), one prospective analysis (level 3), and one meta-analysis (level 2). Due to the heterogeneity of study cases and inclusion criteria, a meta-analysis was not feasible. We also present a novel closure of an anterior skull base defect resulting in a subcutaneous fistula with use of a frontal trephination approach. The frontal sinus trephination should not be regarded as a procedure of the past, as it useful in the armamentarium of the modern sinus and skull base surgeon. This approach provides access for instrumentation for hard-to-reach frontal sinus disease either purely through a trephination approach or as a supplementation to the transnasal endoscopic approach. Evidence supporting frontal sinus trephination is of levels 2, 3, and 4. Level of evidence: NA.

Infected cochlear implant after large-volume nasal irrigation.

OBJECTIVE: A patient with a well-healed, functional cochlear implant (CI) experienced a CI and mastoid infection shortly after initiating large-volume nasal irrigations after sinus surgery. The goal of this report is to bring attention to a rare complication and to question if large-volume nasal irrigation is safe in CI recipients. PATIENTS: Single patient at a tertiary care hospital. INTERVENTIONS: A CI recipient began using large-volume nasal irrigations with saline and budesonide after undergoing sinus surgery. MAIN OUTCOME MEASURES: CI infection and mastoiditis. RESULTS: Two weeks after starting nasal irrigations, the patient presented with mastoiditis and CI infection. Mastoid and intranasal middle meatal cultures both grew Group A streptococcus. CONCLUSION: Large-volume nasal irrigations may be related to our patient's CI infection, ultimately leading to explantation. Though a causal relationship cannot be definitively proven, awareness of this potential safety issue should be disseminated.

Updates in reconstruction of skull base defects.

PURPOSE OF REVIEW: Skull base surgery has undergone a fundamental transformation with the development and rapid adoption of endoscopic endonasal expanded approaches. Defects created from these newer approaches have necessitated an evolution of novel reconstructive techniques, which are reviewed here. RECENT FINDINGS: New reconstructive techniques continue to be developed for repairing surgical defects from endoscopic endonasal skull base resections. Improvisations also allow well known flaps to be used in these approaches. Long term outcomes from repair using some of these techniques are now becoming available. SUMMARY: Endoscopic resection of previously unapproachable skull base lesions has become possible with advancements in technology, as well as reconstructive methods. These newer techniques may offer improved outcomes and lower morbidity over conventional surgery.

Perplexing lesions of the sinonasal cavity and skull base: IgG4-related and similar inflammatory diseases.

OBJECTIVE: IgG4-related disease (IgG4RD) causing sinonasal and skull base pathology is uncommonly described. We present a series of suspected IgG4RD patients, with a pertinent review of the literature to highlight diagnostic challenges. STUDY DESIGN: Case series. SETTING: Academic tertiary care center. SUBJECTS AND METHODS: Case series of patients with IgG4RD or suspected IgG4RD involving the sinonasal cavity and skull base. RESULTS: We present 4 patients with atypical sinonasal and/or skull base disease who were noted to have IgG4-positive plasma cell infiltration on immunohistochemistry of biopsy specimens. IgG4RD, a recently described entity affecting multiple organs, is characterized by lymphoplasmacytic infiltration and often elevated serum IgG4. IgG4RD can masquerade as malignancy or infection but responds to glucocorticosteroid and immunosuppressant therapy. IgG4RD has been infrequently reported presenting as sinonasal or skull base lesions, and definitive diagnostic criteria for these regions are not established. In our series, IgG4RD was suspected in all 4 patients, but only 1 met all current criteria for definitive diagnosis. All 4 patients, however, responded to corticosteroid therapy, and 1 was placed on long-term azathioprine. CONCLUSION: IgG4RD is rarely described in the sinonasal cavity and skull base, and specific diagnostic criteria for such disease have not been defined. We present a series of patients with IgG4-positive plasma cell inflammatory pathology who were suspected to have IgG4RD. Our series highlights diagnostic challenges associated with these patients. Tumefactive and destructive sinonasal-skull base lesions with a plasma cell-rich infiltrate should incite suspicion of IgG4RD, and immunohistochemistry for IgG4-positive plasma cells should be performed.

Laryngeal hibernoma: case series of a rare tumor.

BACKGROUND: Hibernomas are rare, benign tumors of brown adipose tissue uncommonly found in the head and neck. METHODS: A review of the English-language literature was conducted for this study. We present a series of 2 laryngeal hibernomas treated with transoral laser microsurgical resection at a tertiary referral center over a period of 18 years. RESULTS: Only 2 cases of laryngeal hibernoma have been previously described in the literature. Two additional cases were encountered at our institution. Preoperative imaging demonstrated a well-circumscribed neoplasm with fat density compatible with lipoma, but internal heterogeneity and vascularity seen in the context of liposarcoma. Transoral laser microsurgical resection was successfully performed in each case. CONCLUSION: Despite unique radiographic features, hibernomas are difficult to distinguish from well-differentiated liposarcoma and lipoma variants without pathologic correlation. Complete surgical resection is indicated. In our experience, transoral laser microsurgical excision of laryngeal hibernomas is a safe, effective treatment modality with little associated morbidity.

Sinonasal phosphaturic mesenchymal tumor: Case report and systematic review.

We report a case of sinonasal phosphaturic mesenchymal tumor (PMT) and conduct a systematic review of the literature to highlight a unique paraneoplastic syndrome associated with PMT. We used English language publications from Medline and Cochrane databases (1970-2013) as data sources. A systematic review of the literature was conducted. All reported cases of head and neck PMTs were included. The presence or absence of the associated paraneoplastic syndrome was noted. We found 33 cases of PMT in the head and neck reported in the literature, 17 of which occurred in the sinonasal area. Approximately 5% of all PMTs are located in the head and neck. Just greater than half are concentrated in the sinonasal area, and the remaining involve various bony and soft tissue structures of the head and neck. PMT is sometimes associated with a paraneoplastic syndrome of tumor-induced (oncogenic) osteomalacia (TIO) causing bone pain, muscle weakness, and pathologic fractures. We present the 18th reported case of sinonasal PMT. A smooth mucosa-covered midline intraseptal mass filling the posterior nasal cavity with destruction and erosion of the skull base was found in an adult male. The patient underwent successful endoscopic resection with wide negative margins and is without recurrence at 24-month follow-up. PMT is a benign, locally aggressive tumor with rare malignant transformation. Knowledge of the bony invasion and destruction caused by this tumor is essential in planning surgical resection with wide negative margins. Familiarity with the associated TIO is essential to investigate for and manage any associated bony morbidity.

Abducens palsy after lumbar drain placement: a rare complication in endoscopic skull base surgery.

OBJECTIVES/HYPOTHESIS: To study reports of abducens nerve palsy following dural puncture procedures and to discuss possible etiologic theories, treatment, and prognosis. STUDY DESIGN: Systematic review of peer-reviewed literature. METHODS: A systematic literature review was conducted (PubMed, 1950 to September 2011) for cases of sixth cranial nerve palsy following dural puncture procedures. RESULTS: We report a case of abducens nerve palsy following lumbar drain placement for endoscopic trans-sphenoidal pituitary macroadenoma resection. Sixth nerve palsy was noted immediately after surgery. Postoperative computed tomography and magnetic resonance imaging revealed no injury to the nerve or surrounding structures. A systematic literature review conducted for cases of abducens nerve palsy following dural puncture procedures found 22 studies (17 case reports and five case series). Twenty-eight patients with temporary or permanent abducens nerve palsy were reported. Procedures included diagnostic lumbar puncture, spinal anesthesia, intrathecal catheterization, and shunting. Traction and local ischemia due to intracranial hypotension at the petroclival junction were proposed as causes of palsy. CONCLUSIONS: Lumbar puncture procedures carry a rare risk of abducens nerve palsy from ischemic or traction injury. Routine use of lumbar drain during endoscopic skull base surgery is not without risk, and need for its placement should be carefully determined. Knowledge of such rare complications is helpful in risk-benefit analysis as endoscopic skull base techniques gain popularity.

Update on the management of chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a common disorder characterized by mucosal inflammation of the nose and paranasal sinuses with sinonasal symptoms persisting for greater than 12 weeks. The etiology of CRS is incompletely understood. Current understanding supports inflammation, rather than infection, as the dominant etiologic factor. CRS significantly impacts patients' quality of life and health care expenditure. There is no standard management of CRS. Treatment strategies differ based on divergent etiologies of the various CRS subclasses. Both systemic and topical agents are used. These interventions differ in CRS with nasal polyposis (CRSwNP), CRS without nasal polyposis (CRSsNP) and specific situations such as allergic fungal rhinosinusitis or aspirin-exacerbated respiratory disease. Antibiotics are the most commonly prescribed medication for CRS, but their role in management is not strongly supported by high-level studies. This paper provides a succinct review of the evidence supporting or refuting common therapeutic agents in the management of CRS. Novel and emerging strategies will also be discussed.