The Other Aortic Syndrome-Intramural Hematoma and Neurological Deficit: Case Report.

Introduction: Acute thoracic aortic syndromes are among the most concerning presentations in emergency medicine and are associated with significant morbidity and mortality. Thoracic aortic dissection is most common, followed by penetrating aortic ulcer and, least commonly, intramural hematoma. Case Report: A 67-year-old woman presented to the emergency department with chest and back pain, and sudden onset of paraparesis. Aortic intramural hematoma was diagnosed, and she underwent spinal drain placement with blood pressure control to optimize spinal cord perfusion. Discussion: When neurological deficits are present, rapid diagnosis of spinal ischemia and blood pressure optimization is vital. Spinal drains may be considered as an adjunctive treatment.

A human cadaveric model for venous air embolism tool development.

Purpose: A human cadaveric model combining standard lung protective mechanical ventilation and modified cardiac bypass techniques was developed to allow investigation into automated modes of detection of venous air emboli (VAE) prior to in vivo human or animal investigations. Methods: In this study, in order to create an artificial cardiopulmonary circuit in a cadaver that could mimic VAE physiology, the direction of flow was reversed from conventional cardiac bypass. Saline was circulated in isolation through the heart and lungs as opposed to the peripheral organs by placing the venous cannula into the aorta and the arterial cannula into the inferior vena cava with selective ligation of other vessels. Results: Mechanical ventilation and this reversed cardiac bypass scheme allowed preliminary detection of VAE independently but not in concert in our current simulation scheme due to pulmonary edema in the cadaver. A limited dissection approach was used initially followed by a radical exposure of the great vessels, and both proved feasible in terms of air signal detection. We used electrical impendence as a preliminary tool to validate detection in this cadaveric model however we theorize that it would work for echocardiographic, intravenous ultrasound or other novel modalities as well. Conclusion: A cadaveric model allows monitoring technology development with reduced use of animal and conventional human testing.

Refractory Ventricular Tachycardia and Seizures With Lacosamide Overdose.

We describe a 60-year-old female patient who suffered an apparently intentional overdose of lacosamide and who developed status epilepticus secondary to its toxicity, complicated by refractory ventricular arrhythmia necessitating advanced cardiac life support and percutaneous stellate ganglion blockade. Extracorporeal membrane oxygenation was considered, and arterial and venous small-bore sheaths were placed in order to allow for extracorporeal cardiopulmonary resuscitation if cardiac arrest recurred, but they were not ultimately used. She suffered an embolic left middle cerebral artery stroke but otherwise recovered from the episode. This eventful clinical course highlights the dangers of lacosamide in high doses.

An Integrated Approach to Identify New Anti-Filarial Leads to Treat River Blindness, a Neglected Tropical Disease.

Filarial worms cause multiple debilitating diseases in millions of people worldwide, including river blindness. Currently available drugs reduce transmission by killing larvae (microfilariae), but there are no effective cures targeting the adult parasites (macrofilaricides) which survive and reproduce in the host for very long periods. To identify effective macrofilaricides, we carried out phenotypic screening of a library of 2121 approved drugs for clinical use against adult Brugia pahangi and prioritized the hits for further studies by integrating those results with a computational prioritization of drugs and associated targets. This resulted in the identification of 18 hits with anti-macrofilaricidal activity, of which two classes, azoles and aspartic protease inhibitors, were further expanded upon. Follow up screening against Onchocerca spp. (adult Onchocerca ochengi and pre-adult O. volvulus) confirmed activity for 13 drugs (the majority having IC50 < 10 µM), and a counter screen of a subset against L. loa microfilariae showed the potential to identify selective drugs that prevent adverse events when co-infected individuals are treated. Stage specific activity was also observed. Many of these drugs are amenable to structural optimization, and also have known canonical targets, making them promising candidates for further optimization that can lead to identifying and characterizing novel anti-macrofilarial drugs.

Timing of Postoperative CSF Leak after Endoscopic Skull Base Surgery in Patients with Obstructive Sleep Apnea.

Background There is little data regarding postoperative outcomes of patients with obstructive sleep apnea (OSA) undergoing skull base surgery. The purpose of this study is to determine an association between risk factors and proximity of cerebrospinal fluid (CSF) leak to surgery in patients with OSA undergoing endoscopic skull base surgery. Methods A retrospective review of neurosurgical inpatients, with and without OSA, at a tertiary care institution from 2002 to 2015 that experienced a postoperative CSF leak after undergoing endoscopic skull base surgery. Results Forty patients met inclusion criteria, 12 (30%) with OSA. OSA patients had significantly higher body mass index (BMI; median 39.4 vs. 31.7, p < 0.01) and were more likely to have diabetes (41.7 vs. 10.7%, p = 0.04) than non-OSA patients; otherwise there were no significant differences in clinical comorbidities. No patients restarted positive pressure ventilation (PPV) in the inpatient setting. The type of repair was not a significant predictor of the time from surgery to leak. Patients with OSA experienced postoperative CSF leak 49% sooner than non-OSA patients (Hazard Ratio 1.49, median 2 vs. 6 days, log-rank p = 0.20). Conclusion Patients with OSA trended toward leaking earlier than those without OSA, and no OSA patients repaired with a nasoseptal flap (NSF) had a leak after postoperative day 5. Due to a small sample size this trend did not reach significance. Future studies will help to determine the appropriate timing for restarting PPV in this high risk population. This is important given PPV's significant benefit to the patient's overall health and its ability to lower intracranial pressure.

"Interlocking" Clipping of an Irregular Middle Cerebral Artery Bifurcation Aneurysm: 2-Dimensional Operative Video.

Middle cerebral artery (MCA) aneurysms often have an irregular morphology that might require creative clipping techniques even in the case of small aneurysms. In this video, we illustrate the case of a patient with an incidental but very irregular MCA aneurysm. The presence of 2 separate, asymmetric lobes was dealt with by utilizing the "interlocking" clip technique in which a regular clip is used to obliterate 1 portion of the aneurysm and a fenestrated clip, with the ring of the fenestration circling the body of the first clip, is used to obtain obliteration of the other lobe. This patient also had a contralateral internal carotid artery occlusion, and we discuss the pitfalls of temporary clipping in such a situation.

Endoscopic Endonasal Resection of Orbital Apex Cavernous Hemangioma: 2-Dimensional Operative Video.

A 52-yr-old woman was referred to a tertiary medical center for evaluation of 2 yr of progressive visual symptoms and 1 yr of retro-orbital pressure. Her ophthalmologic exam was unrevealing except for mild asymmetrical impairment in color perception. A gadolinium contrast-enhanced magnetic resonance image of the head showed a left extraconal orbital apex lesion consistent with cavernous hemangioma. Computed tomography reveled bony remodeling of the medial-inferior orbital walls with superior orbital fissure expansion. The lesion was endoscopically resected and confirmed by pathological analysis. The endoscopic approach is demonstrated in detail, including correlation with cadaveric anatomic specimens‡. During the approach, a rescue nasoseptal flap was raised in case the orbit required further support after tumor resection, but was replaced as this was not needed. This patient had a brief period of postoperative diplopia, which resolved 1 wk after surgery. Her subjective visual deficits and pressure have also resolved. Advantages of the endoscopic approach include improved direct visualization of the lesion, lack of external skin incisions, avoidance of significant neurovascular retraction, and shorter hospital stays than alternative orbitotomy or craniotomy approaches. This 4-handed approach demands endoscopic expertise of 2 surgeons, and is often performed by rhinology-neurosurgery or rhinology-ophthalmology surgical teams. The risk of postoperative diplopia should be discussed with the patient during informed consent. ‡ Anatomic specimen photography courtesy Dr Peris-Celda.

Cortical surface intracranial electrodes identify clinically relevant seizures missed on scalp EEG after traumatic intracranial hemorrhage.

Seizures and other electrophysiological disturbances are an under-recognized cause of coma, focal deficits, and prolonged encephalopathy following subdural hematoma evacuation. In these patients, it is possible that seizures remain unrecognized on scalp EEG. It has been shown that a high burden of seizures and other electrophysiological disturbances exist following surgical evacuation and underlie the encephalopathy commonly seen in this patient population, predisposing them to medical complications and confounding estimates of prognosis. As part of a research protocol, we are performing intraoperative placement of cortical surface (non-parenchyma penetrating) intracranial EEG on patients who present after trauma and require emergent decompressive hemicraniectomy. In this case report of a patient with high-velocity traumatic epidural, subdural, and subarachnoid hemorrhages, we identified frequent non-convulsive seizures or seizure-like SIRPIDs with intracranial cortical surface monitoring that were not identified on simultaneous scalp EEG. Stimulation consistently triggered these electrographic seizures in addition to rhythmic lateralized periodic discharges. His mental status improved rapidly after resolution of these electrographic seizures shortly after increasing antiseizure medications, suggesting that they may have been contributing to his encephalopathy. More research is needed to determine the frequency of this phenomenon and determine whether treatment of such seizures improves patient outcomes.

Repurposing auranofin as a lead candidate for treatment of lymphatic filariasis and onchocerciasis.

Two major human diseases caused by filariid nematodes are onchocerciasis, or river blindness, and lymphatic filariasis, which can lead to elephantiasis. The drugs ivermectin, diethylcarbamazine (DEC), and albendazole are used in control programs for these diseases, but are mainly effective against the microfilarial stage and have minimal or no effect on adult worms. Adult Onchocerca volvulus and Brugia malayi worms (macrofilariae) can live for up to 15 years, reproducing and allowing the infection to persist in a population. Therefore, to support control or elimination of these two diseases, effective macrofilaricidal drugs are necessary, in addition to current drugs. In an effort to identify macrofilaricidal drugs, we screened an FDA-approved library with adult worms of Brugia spp. and Onchocerca ochengi, third-stage larvae (L3s) of Onchocerca volvulus, and the microfilariae of both O. ochengi and Loa loa. We found that auranofin, a gold-containing drug used for rheumatoid arthritis, was effective in vitro in killing both Brugia spp. and O. ochengi adult worms and in inhibiting the molting of L3s of O. volvulus with IC50 values in the low micromolar to nanomolar range. Auranofin had an approximately 43-fold higher IC50 against the microfilariae of L. loa compared with the IC50 for adult female O. ochengi, which may be beneficial if used in areas where Onchocerca and Brugia are co-endemic with L. loa, to prevent severe adverse reactions to the drug-induced death of L. loa microfilariae. Further testing indicated that auranofin is also effective in reducing Brugia adult worm burden in infected gerbils and that auranofin may be targeting the thioredoxin reductase in this nematode.

Utilization of computer processed high definition video imaging for measuring motility of microscopic nematode stages on a quantitative scale: "The Worminator".

A major hindrance to evaluating nematode populations for anthelmintic resistance, as well as for screening existing drugs, new compounds, or bioactive plant extracts for anthelmintic properties, is the lack of an efficient, objective, and reproducible in vitro assay that is adaptable to multiple life stages and parasite genera. To address this need we have developed the "Worminator" system, which objectively and quantitatively measures the motility of microscopic stages of parasitic nematodes. The system is built around the computer application "WormAssay", developed at the Center for Discovery and Innovation in Parasitic Diseases at the University of California, San Francisco. WormAssay was designed to assess motility of macroscopic parasites for the purpose of high throughput screening of potential anthelmintic compounds, utilizing high definition video as an input to assess motion of adult stage (macroscopic) parasites (e.g. Brugia malayi). We adapted this assay for use with microscopic parasites by modifying the software to support a full frame analysis mode that applies the motion algorithm to the entire video frame. Thus, the motility of all parasites in a given well are recorded and measured simultaneously. Assays performed on third-stage larvae (L3) of the bovine intestinal nematode Cooperia spp., as well as microfilariae (mf) of the filarioid nematodes B. malayi and Dirofilaria immitis, yielded reproducible dose responses using the macrocyclic lactones ivermectin, doramectin, and moxidectin, as well as the nicotinic agonists, pyrantel, oxantel, morantel, and tribendimidine. This new computer based-assay is simple to use, requires minimal new investment in equipment, is robust across nematode genera and developmental stage, and does not require subjective scoring of motility by an observer. Thus, the "Worminator" provides a relatively low-cost platform for developing genera- and stage-specific assays with high efficiency and reproducibility, low labor input, and yields objective motility data that is not subject to scorer bias.

WormAssay: a novel computer application for whole-plate motion-based screening of macroscopic parasites.

Lymphatic filariasis is caused by filarial nematode parasites, including Brugia malayi. Adult worms live in the lymphatic system and cause a strong immune reaction that leads to the obstruction of lymph vessels and swelling of the extremities. Chronic disease leads to the painful and disfiguring condition known as elephantiasis. Current drug therapy is effective against the microfilariae (larval stage) of the parasite, but no drugs are effective against the adult worms. One of the major stumbling blocks toward developing effective macrofilaricides to kill the adult worms is the lack of a high throughput screening method for candidate drugs. Current methods utilize systems that measure one well at a time and are time consuming and often expensive. We have developed a low-cost and simple visual imaging system to automate and quantify screening entire plates based on parasite movement. This system can be applied to the study of many macroparasites as well as other macroscopic organisms.