Open and Endoscopic Endonasal Optic Nerve Decompression for Craniofacial Fibrous Dysplasia in an Adolescent: 2-Dimensional Operative Video.

Craniofacial fibrous dysplasia (CFFD) is a benign, bony disease that may affect the skull base.1,2 Most cases are asymptomatic and observed; however, advanced disease can present with cranial neuropathy or craniofacial deformity requiring intervention.3-5 A 16-year-old adolescent girl with known CFFD involving the sphenoid and frontal bones with severe bilateral optic canal narrowing developed progressive right eye visual decline and frontal cosmetic deformity. Visual acuity worsened oculus dextrus (OD) to 20/30 with a new superior nasal scotoma and 20% loss in the retinal nerve fiber layer and remained oculus sinister (OS) 20/20. The patient was recommended a staged subfrontal craniotomy for right optic decompression and simultaneous correction cosmetic deformity followed by endonasal right optic decompression. On postoperative day one, visual acuity OD improved to 20/20; however, she developed OS visual decline to 20/800. Curiously, there were no episodes of intraoperative hypotension or additional iatrogenic compression. Use of methylprednisolone led to improvement OS 20/400. Given persistent visual decline, urgent second stage endonasal bilateral optic nerve decompression, rather than unilateral, was performed. Postoperatively, vision improved to OS 20/200. At one month, her vision improved to OD 20/15 and OS returned to 20/20 with a paracentral scotoma and 29% decline in left retinal nerve fiber layer with further improvement anticipated. This video describes a multidisciplinary, multistaged approach in treatment of optic nerve compression due to CFFD in addition to the management of unanticipated contralateral visual decline. The patient consented to the procedure and publication of her image. No Institutional Review Board/ethics committee approval was necessary for this case report.

Use of a Pericranial Flap Technique for Deep Brain Stimulation Hardware Protection and Improved Cosmesis.

OBJECTIVES: Deep brain stimulation (DBS) has become an established neuromodulation therapy; however, surgical site complications such as hardware skin erosion remain an important risk and can predispose to infection, requiring explantation of the system. Nuances of surgical technique can affect wound healing, cosmetic outcome, comfort, and risk of infection. In this study, we describe our experience with a layered closure technique using a vascularized pericranial flap for improving cosmesis and protection of the implanted hardware against skin erosion and infection. MATERIALS AND METHODS: We retrospectively reviewed 636 individuals (746 lead implantations) who underwent DBS surgery by a single academic neurosurgeon between 2001 and 2020. A layered pericranial flap closure technique for the burr-hole and connector sites was instituted in 2015. We assessed the effects of a multimodal infection prevention approach that included the pericranial flap on hardware complication rates compared with the premultimodality cohort, and we report the nuances of the technique. RESULTS: In our institutional experience, we found that implementation of a pericranial flap closure technique can enhance the subjective cosmetic result at the burr-hole cover site and increase patient comfort and satisfaction. In addition, we found a decrease in hardware infection rates in the current cohort with a multimodal infection prevention regimen that includes the pericranial-flap technique (n = 256, 2015-2020 period) to 1.2% (p = 0.006), from 6.9% in the earlier cohort (n = 490, 2001-2015 period). CONCLUSIONS: The report highlights the potential of a pericranial-flap closure technique as a surgical adjunct to improve DBS surgical site healing and cosmesis and may, as part of a multimodal strategy, contribute to decreased risk of skin breakdown and hardware infection.

Recrudescent infection after deep brain stimulator reimplantation.

OBJECTIVE: The efficacy of deep brain stimulation (DBS) in treating the symptoms of movement disorders can be life changing for patients. Thus, the 5%-15% incidence of stimulator-related infection requiring removal of the device can be particularly disheartening. Although DBS system reimplantation is generally successful, this is not always the case. The literature is replete with publications describing the incidence of infection and the associated features. However, the literature is sparse in terms of information on the incidence of recurrent or recrudescent infection after system reimplantation. The goal of this paper was to evaluate factors leading to unsuccessful reimplantation of a DBS system following initial infection. METHODS: Data were reviewed for all DBS procedures performed by one surgeon (K.L.H.) over 19 years including the infectious agent, location of infection, treatment regimen, and subsequent reimplantation of a DBS system and long-term outcome. RESULTS: In this series of 558 patients who had undergone DBS surgery, 37 (6.6%) subsequently developed an infection. Infections with methicillin-sensitive Staphylococcus aureus, Enterobacter species, or coagulase-negative staphylococci were predominant. Four patients had cerebritis, one had meningitis, and the rest had soft tissue infections of the pocket or scalp. All had their entire DBS system explanted, followed by 4-6 weeks of intravenous antibiotics and surveillance for recrudescence for an additional period of at least 30 days. Twenty-five patients subsequently underwent DBS system reimplantation, and the procedure was successful in 22. Three of the 4 patients with cerebritis developed a subsequent wound infection after system reimplantation. None of the other 22 patients developed a recurrence. The odds ratio for developing a recurrent infection after cerebritis was 28.5 (95% CI 1.931-420.5, p = 0.007). CONCLUSIONS: This study, the largest series of DBS system reimplantations following infection, demonstrated that most patients can have successful reimplantations without recurrent infection. However, patients who have had DBS-related cerebritis have a nearly 30-fold increased risk of developing reinfection after reimplantation. Alternative strategies for these patients are discussed.

Adverse effects and antibody titers in response to the BNT162b2 mRNA COVID-19 vaccine in a prospective study of healthcare workers.

BACKGROUND: mRNA COVID-19 vaccines are playing a key role in controlling the COVID-19 pandemic. The relationship between post-vaccination symptoms and strength of antibody responses is unclear. OBJECTIVE: To determine whether adverse effects caused by vaccination with the Pfizer/BioNTech BNT162b2 vaccine are associated with the magnitude of vaccine-induced antibody levels. DESIGN: Single center, prospective, observational cohort study. SETTING: Participants worked at Walter Reed National Military Medical Center and were seen monthly at the Naval Medical Research Center Clinical Trials Center. PARTICIPANTS: Generally healthy adults that were not severely immunocompromised, had no history of COVID-19, and were seronegative for SARS-CoV-2 spike protein prior to vaccination. MEASURES: Severity of vaccine-associated symptoms was obtained through participant completed questionnaires. Testing for IgG antibodies against SARS-CoV-2 spike protein and receptor binding domain was conducted using microsphere-based multiplex immunoassays. RESULTS: 206 participants were evaluated (69.4% female, median age 41.5 years old). We found no correlation between vaccine-associated symptom severity scores and vaccine-induced antibody titers one month after vaccination. We also observed that 1) post-vaccination symptoms were inversely correlated with age and weight and more common in women, 2) systemic symptoms were more frequent after the second vaccination, 3) high symptom scores after first vaccination were predictive of high symptom scores after second vaccination, and 4) older age was associated with lower titers. LIMITATIONS: Study only observes antibody responses and consists of healthy participants. CONCLUSIONS: Lack of post-vaccination symptoms following receipt of the BNT162b2 vaccine does not equate to lack of vaccine-induced antibodies one month after vaccination. This study also suggests that it may be possible to design future mRNA vaccines that confer robust antibody responses with lower frequencies of vaccine-associated symptoms. FUNDING: This study was executed by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed by the Uniformed Services University of the Health Sciences (USUHS) through a cooperative agreement by the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). This project has been funded by the Defense Health Program, U.S. DoD, under award HU00012120067. Project funding for JHP was in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The funding bodies have had no role in the study design or the decision to submit the manuscript for publication.

The Poised Cannula Technique Reduces the Stereotactic Error of the Fiducial-Less Frameless DBS Procedure.

BACKGROUND: In this study, we describe a technique of optimizing the accuracy of frameless deep brain stimulation (DBS) lead placement through the use of a cannula poised at the entry to predict the location of the fully inserted device. This allows real-time correction of error prior to violation of the deep gray matter. METHODS: We prospectively gathered data on radial error during the operative placements of 40 leads in 28 patients using frameless fiducial-less DBS surgery. Once the Nexframe had been aligned to target, a cannula was inserted through the center channel of the BenGun until it traversed the pial surface and a low-dose O-arm spin was obtained. Using 2 points along the length of the imaged cannula, a trajectory line was projected to target depth. If lead location could be improved, the cannula was inserted through an alternate track in the BenGun down to target depth. After intraoperative microelectrode recording and clinical assessment, another O-arm spin was obtained to compare the location of the inserted lead with the location predicted by the poised cannula. RESULTS: The poised cannula projection and the actual implant had a mean radial discrepancy of 0.75 ± 0.64 mm. The poised cannula projection identified potentially clinically significant errors (avg 2.07 ± 0.73 mm) in 33% of cases, which were reduced to a radial error of 1.33 ± 0.66 mm (p = 0.02) after correction using an alternative BenGun track. The final target to implant error for all 40 leads was 1.20 ± 0.52 mm with only 2.5% of errors being >2.5 mm. CONCLUSION: The poised cannula technique results in a reduction of large errors (>2.5 mm), resulting in a decline in these errors to 2.5% of implants as compared to 17% in our previous publication using the fiducial-less method and 4% using fiducial-based methods of DBS lead placement.

Functional Assessment of 2,177 U.S. and International Drugs Identifies the Quinoline Nitroxoline as a Potent Amoebicidal Agent against the Pathogen Balamuthia mandrillaris.

Balamuthia mandrillaris is a pathogenic free-living amoeba that causes a rare but almost always fatal infection of the central nervous system called granulomatous amoebic encephalitis (GAE). Two distinct forms of B. mandrillaris-a proliferative trophozoite form and a nonproliferative cyst form, which is highly resistant to harsh physical and chemical conditions-have been isolated from environmental samples worldwide and are both observed in infected tissue. Patients suffering from GAE are typically treated with aggressive and prolonged multidrug regimens that often include the antimicrobial agents miltefosine and pentamidine isethionate. However, survival rates remain low, and studies evaluating the susceptibility of B. mandrillaris to these compounds and other potential therapeutics are limited. To address the need for more-effective treatments, we screened 2,177 clinically approved compounds for in vitro activity against B. mandrillaris The quinoline antibiotic nitroxoline (8-hydroxy-5-nitroquinoline), which has safely been used in humans to treat urinary tract infections, was identified as a lead compound. We show that nitroxoline inhibits both trophozoites and cysts at low micromolar concentrations, which are within a pharmacologically relevant range. We compared the in vitro efficacy of nitroxoline to that of drugs currently used in the standard of care for GAE and found that nitroxoline is the most potent and selective inhibitor of B. mandrillaris tested. Furthermore, we demonstrate that nitroxoline prevents B. mandrillaris-mediated destruction of host cells in cultured fibroblast and primary brain explant models also at pharmacologically relevant concentrations. Taken together, our findings indicate that nitroxoline is a promising candidate for repurposing as a novel treatment of B. mandrillaris infections.IMPORTANCEBalamuthia mandrillaris is responsible for hundreds of reported cases of amoebic encephalitis, the majority of which have been fatal. Despite being an exceptionally deadly pathogen, B. mandrillaris is understudied, leaving many open questions regarding epidemiology, diagnosis, and treatment. Due to the lack of effective drugs to fight B. mandrillaris infections, mortality rates remain high even for patients receiving intensive care. This report addresses the need for new treatment options through a drug repurposing screen to identify novel B. mandrillaris inhibitors. The most promising candidate identified was the quinoline antibiotic nitroxoline, which has a long history of safe use in humans. We show that nitroxoline kills B. mandrillaris at pharmacologically relevant concentrations and exhibits greater potency and selectivity than drugs commonly used in the current standard of care. The findings that we present demonstrate the potential of nitroxoline to be an important new tool in the treatment of life-threatening B. mandrillaris infections.

Determination of the cyanide metabolite 2-aminothiazoline-4-carboxylic acid in urine and plasma by gas chromatography-mass spectrometry.

The cyanide metabolite 2-aminothiazoline-4-carboxylic acid (ATCA) is a promising biomarker for cyanide exposure because of its stability and the limitations of direct determination of cyanide and more abundant cyanide metabolites. A simple, sensitive, and specific method based on derivatization and subsequent gas chromatography-mass spectrometry (GC-MS) analysis was developed for the identification and quantification of ATCA in synthetic urine and swine plasma. The urine and plasma samples were spiked with an internal standard (ATCA-d(2)), diluted, and acidified. The resulting solution was subjected to solid phase extraction on a mixed-mode cation exchange column. After elution and evaporation of the solvent, a silylating agent was used to derivatize the ATCA. Quantification of the derivatized ATCA was accomplished on a gas chromatograph with a mass selective detector. The current method produced a coefficient of variation of less than 6% (intra- and interassay) for two sets of quality control (QC) standards and a detection limit of 25 ng/ml. The applicability of the method was evaluated by determination of elevated levels of ATCA in human urine of smokers in relation to non-smokers for both males and females.