Faculty Bibliography

Direct access through the sinuses and nasopharyngeal mucosa in the endoscopic endonasal approach (EEA) raises concern for a contaminated operative environment and subsequent infection. The reported rate of meningitis in endoscopic endonasal skull base surgery in the literature ranges from 0.7 to 3.0% [1, 2]. The only factor identified as being independently associated with meningitis in a statistically significant manner is cerebrospinal fluid (CSF) leak [1-5]. However, many centers performing high volume of EEAs use postoperative antibiotic coverage independent of the presence intraoperative or postoperative CSF leak. Furthermore, while meningitis remains a severe concern, most centers use postoperative gram-positive coverage to prevent toxic shock syndrome caused by Staphylococcus aureus infection in the setting of prolonged nasal packing. There are currently a multitude of approaches regarding perioperative antibiotic coverage in EEAs [1-4]. Given the lack of consensus in the literature and our experience regarding the benefit of discontinuation of prolonged prophylactic antibiotics throughout the breadth of neurosurgical procedures, we sought to analyze the need for postoperative antibiotics in EEAs further. As such, we performed a prospective analysis compared with a retrospective cohort to delineate whether discontinuation of postoperative antibiotics leads to a change in the rate of postoperative infections. The retrospective cohort consisted of patients who underwent an EEA from January 1, 2013 to May 31, 2019. These patients all received postoperative antibiotics while nasal packing was in place (median 7 days). Starting on April 1, 2019 until August 1, 2019, we discontinued postoperative antibiotic use. Patients from this group made up the prospective cohort. The retrospective cohort had 315 patients (66% pituitary macroadenomas vs. 7% microadenomas, 4% meningiomas, 4% craniopharyngiomas, 4% chordomas, and 15% others) while the prospective group had 23 patients (57% pituitary macroadenomas, 30% craniopharyngiomas, 8% meningiomas/chordomas, and 5% others). The primary endpoint was rate of postoperative infections and specifically, meningitis and multidrug resistant organism (MDRO) infections. There was no statistically significant difference in the use of nasal packing (p = 0.085), intraoperative CSF leak (p = 0.133), and postoperative CSF leak (p = 0.507) between the two groups. There was also no significant difference in the number of patients with positive preoperative MSSA and MRSA nasal swabs (p = 0.622). There was a significant decrease in the number of patients discharged with antibiotics (55.1% in the retrospective and 4.5% in the prospective group, p = 0.000). The number of patients with positive blood cultures (p = 0.701) and positive urine cultures (p = 0.691) did not differ significantly between the two groups. Finally, there was no statistically significant difference in postoperative CSF infections (p = 0.34) or MDRO infections (0.786) between the two groups. We describe promising preliminary results that demonstrate that discontinuation of postoperative antibiotics in EEAs do not lead to a statistically significant increase in the rate of postoperative CSF or MDRO infections. The previous algorithm for postoperative antibiotic coverage in our center, like many centers, called for gram-positive coverage, which may have contributed to the overall preponderance of gram-negative meningitis cases in this cohort

Enteroviruses (EV) are responsible for a large number of meningoencephalitis cases, especially in children. The objective of this study was to identify modes of diagnosis including the significance of respiratory and cerebrospinal fluid samples, associated clinical characteristics, inpatient management, and outcome of individuals with EV infections of the central nervous system (CNS). Electronic medical records of individuals with enterovirus infections of the CNS who presented to the Columbia University Irving Medical Center and Children's Hospital of New York between January 1, 2012 and December 31, 2017 were reviewed retrospectively for demographic, epidemiological, and clinical data. The median age overall was 1.7 months (interquartile range 14 years) and most (62.4%) were male. The majority of CNS infections presented as meningitis (95.7%) and occurred in the summer (45.2%) and fall seasons (37.6%). Eighty-five cases (91.4%) demonstrated EV positivity in cerebrospinal fluid, thirty cases (32.3%) exhibited both cerebrospinal fluid and respiratory positivity, and eight cases (8.6%) exhibited respiratory positivity with coinciding neurological findings. Eighty-nine individuals overall (95.7%) received antibiotics and 37 (39.8%) received antiviral treatment. All surviving individuals had favorable Modified Rankin Scores (MRS) within the zero to two ranges upon discharge. Testing respiratory samples in addition to cerebrospinal fluid was found to be an important diagnostic tool in EV-associated cases. While clinical outcomes were favorable for an overwhelming majority of cases, etiological understanding of CNS infections is essential for identifying ongoing and changing epidemiological patterns and aid in improving the diagnosis and treatment.

OBJECTIVES/OBJECTIVE:To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. DESIGN/METHODS:A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. METHODS:The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS:The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 52 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 49 research priorities were identified. CONCLUSIONS:A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.

PURPOSE/OBJECTIVE:This study reports the ophthalmic and genetic findings of a Cameroonian patient with autosomal recessive retinitis pigmentosa (arRP) caused by a novel Receptor Expression Enhancing Protein 6 (REEP6) homozygous mutation. PATIENT AND METHODS/METHODS:A 33-year-old man underwent comprehensive ophthalmic examinations, including visual acuity measurements, dilated fundus imaging, electroretinography (ERG), and spectral-domain optical coherence tomography (SD-OCT). Short-wavelength fundus autofluorescence (SW-AF) and near-infrared fundus autofluorescence (NIR-AF) were also evaluated. Whole exome sequencing (WES) was used to identify potential pathogenic variants. RESULTS:Fundus examination revealed typical RP findings with additional temporal ten micron yellow dots. SD-OCT imaging revealed cystoid macular edema and perifoveal outer retinal atrophy with centrally preserved inner segment ellipsoid zone (EZ) bands. Hyperreflective spots were seen in the inner retinal layers. On SW-AF images, a hypoautofluorescent area in the perifoveal area was observed. NIR-AF imaging revealed an irregularly shaped hyperautofluorescent ring. His visual acuity was mildly affected. ERG showed undetectable rod responses and intact cone responses. Genetic testing via WES revealed a novel homozygous mutation (c.295G>A, p.Glu99Lys) in the gene encoding REEP6, which is predicted to alter the charge in the transmembrane helix. CONCLUSIONS:This report is not only the first description of a Cameroonian patient with arRP associated with a REEP6 mutation, but also this particular genetic alteration. Substitution of p.Glu99Lys in REEP6 likely disrupts the interactions between REEP6 and the ER membrane. NIR-AF imaging may be particularly useful for assessing functional photoreceptor cells and show an "avocado" pattern of hyperautofluorescence in patients with the REEP6 mutation.

Background and Purpose- It is unknown whether admission systolic blood pressure (SBP) differs among causes of intracerebral hemorrhage (ICH). We sought to elucidate an association between admission BP and ICH cause. Methods- We compared admission SBP across ICH causes among patients in the Cornell Acute Stroke Academic Registry, which includes all adults with ICH at our center from 2011 through 2017. Trained analysts prospectively collected demographics, comorbidities, and admission SBP, defined as the first recorded value in the emergency department or on transfer from another hospital. ICH cause was adjudicated by a panel of neurologists using the SMASH-U criteria. We used ANOVA to compare mean admission SBP among ICH causes. We used multiple linear regression to adjust for age, sex, race, Glasgow Coma Scale score, and hematoma size. In secondary analyses, we compared hourly SBP measurements during the first 72 hours after admission, using mixed-effects linear models adjusted for the covariates above plus antihypertensive agents. Results- Among 484 patients with ICH, admission SBP varied significantly across ICH causes, ranging from 138 (±24) mm Hg in those with structural vascular lesions to 167 (±35) mm Hg in those with hypertensive ICH (P<0.001). The mean admission SBP in hypertensive ICH was 17 (95% CI, 11-24) mm Hg higher than in ICH of all other causes combined. These differences remained significant after adjustment for age, sex, race, Glasgow Coma Scale score, and hematoma size (P<0.001), and this persisted throughout the first 72 hours of hospitalization (P<0.001). Conclusions- In a single-center ICH registry, SBP varied significantly among ICH causes, both on admission and during hospitalization. Our results suggest that BP in the acute post-ICH setting is at least partly associated with ICH cause rather than simply representing a physiological reaction to the ICH itself.

A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) previously published in 2014 [Lefaucheur et al., Clin Neurophysiol 2014;125:2150-206]. These updated recommendations take into account all rTMS publications, including data prior to 2014, as well as currently reviewed literature until the end of 2018. Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the painful side for neuropathic pain; HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) using a figure-of-8 or a H1-coil for depression; low-frequency (LF) rTMS of contralesional M1 for hand motor recovery in the post-acute stage of stroke. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia; HF-rTMS of bilateral M1 regions or the left DLPFC for improving motor impairment or depression, respectively, in Parkinson's disease; HF-rTMS of ipsilesional M1 for promoting motor recovery at the post-acute stage of stroke; intermittent theta burst stimulation targeted to the leg motor cortex for lower limb spasticity in multiple sclerosis; HF-rTMS of the right DLPFC in posttraumatic stress disorder; LF-rTMS of the right inferior frontal gyrus in chronic post-stroke non-fluent aphasia; LF-rTMS of the right DLPFC in depression; and bihemispheric stimulation of the DLPFC combining right-sided LF-rTMS (or continuous theta burst stimulation) and left-sided HF-rTMS (or intermittent theta burst stimulation) in depression. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The current recommendations are based on the differences reached in therapeutic efficacy of real vs. sham rTMS protocols, replicated in a sufficient number of independent studies. This does not mean that the benefit produced by rTMS inevitably reaches a level of clinical relevance.

OBJECTIVES/OBJECTIVE:To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. DESIGN/METHODS:A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. METHODS:The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. RESULTS:The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified. CONCLUSIONS:A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.

Although abnormally folded tau protein has been found to self-propagate from neuron to connected neuron, similar propagation through human brain networks has not been fully documented. We studied tau propagation in the left-hemispheric syntactic network, which is composed of an anterior frontal node and a posterior temporal node, connected by the white matter of the left arcuate fasciculus. This network is affected in non-fluent variant primary progressive aphasia, a neurodegenerative disorder with tau accumulation. Methods: Eight patients with non-fluent variant primary progressive aphasia (age 67.0 ± 7.4 years, 4 women) and eight healthy controls (age 69.6 ± 7.0 years, 4 women) were scanned with ¹⁸F-AV-1451 tau PET, to determine tau deposition in the brain, and with MRI, to determine the fractional anisotropy of the arcuate fasciculus. Normal syntactic network characteristics were confirmed with structural MRI diffusion imaging in our healthy controls and with BOLD functional imaging in 35 healthy participants from the Alzheimer's Disease Neuroimaging Initiative database. Results: Language scores in patients indicated dysfunction of the anterior node. ¹⁸F-AV-1451 deposition was greatest in the two nodes of the syntactic network. The left arcuate fasciculus had decreased fractional anisotropy, particularly near the anterior node. Normal MRI structural connectivity from an area similar to the one containing tau in the anterior, frontal, node projected to an area similar to the one containing tau in the patients, in the posterior, temporal, node. Conclusion: Tau accumulation likely started in the more affected anterior node and, at the stage of the disease when we studied these patients, appeared as well in the brain region, in the temporal lobe, spatially separate but most connected with it. The arcuate fasciculus, connecting both of them, was most severely affected anteriorly, as would correspond to the loss of axons from the anterior node. These findings are suggestive of tau propagation from node to connected node in a natural human brain network and lend support to the idea that neurons that wire together, die together.