What Should a Clinician Do When Spreading Depolarizations are Observed in a Patient?

The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in the September of 2018 devoted a section to address the question, "What should a clinician do when spreading depolarizations are observed in a patient?" Discussants represented a wide range of expertise, including neurologists, neurointensivists, neuroradiologists, neurosurgeons, and pre-clinical neuroscientists, to provide both clinical and basic pathophysiology perspectives. A draft summary of viewpoints offered was then written by a multidisciplinary writing group of iCSD members, based on a transcript of the session. Feedback of all discussants was formally collated, reviewed, and incorporated into the final document which was subsequently approved by all authors.

Which Spreading Depolarizations Are Deleterious To Brain Tissue?

Spreading depolarizations (SDs) are profound disruptions of cellular homeostasis that slowly propagate through gray matter and present an extraordinary metabolic challenge to brain tissue. Recent work has shown that SDs occur commonly in human patients in the neurointensive care setting and have established a compelling case for their importance in the pathophysiology of acute brain injury. The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in September of 2018 included a discussion session focused on the question of "Which SDs are deleterious to brain tissue?" iCSD is attended by investigators studying various animal species including invertebrates, in vivo and in vitro preparations, diseases of acute brain injury and migraine, computational modeling, and clinical brain injury, among other topics. The discussion included general agreement on many key issues, but also revealed divergent views on some topics that are relevant to the design of clinical interventions targeting SDs. A draft summary of viewpoints offered was then written by a multidisciplinary writing group of iCSD members, based on a transcript of the session. Feedback of all discussants was then formally collated, reviewed and incorporated into the final document. It is hoped that this report will stimulate collection of data that are needed to develop a more nuanced understanding of SD in different pathophysiological states, as the field continues to move toward effective clinical interventions.

Microstructured elastomeric surfaces with reversible adhesion and examples of their use in deterministic assembly by transfer printing.

Reversible control of adhesion is an important feature of many desired, existing, and potential systems, including climbing robots, medical tapes, and stamps for transfer printing. We present experimental and theoretical studies of pressure modulated adhesion between flat, stiff objects and elastomeric surfaces with sharp features of surface relief in optimized geometries. Here, the strength of nonspecific adhesion can be switched by more than three orders of magnitude, from strong to weak, in a reversible fashion. Implementing these concepts in advanced stamps for transfer printing enables versatile modes for deterministic assembly of solid materials in micro/nanostructured forms. Demonstrations in printed two- and three-dimensional collections of silicon platelets and membranes illustrate some capabilities. An unusual type of transistor that incorporates a printed gate electrode, an air gap dielectric, and an aligned array of single walled carbon nanotubes provides a device example.

NEWTON-2 Cisternal (Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage): A Phase 2, Multicenter, Randomized, Open-Label Safety Study of Intracisternal EG-1962 in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: A sustained release microparticle formulation of nimodipine (EG-1962) was developed for treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE: To assess safety, tolerability, and pharmacokinetics of intracisternal EG-1962 in an open-label, randomized, phase 2 study of up to 12 subjects. METHODS: Subjects were World Federation of Neurological Surgeons grades 1 to 2, modified Fisher grades 2 to 4, and underwent aneurysm clipping within 48 h of aSAH. EG-1962, containing 600 mg nimodipine, was administered into the basal cisterns. Outcome on the extended Glasgow Outcome Scale (eGOS), pharmacokinetics, delayed cerebral ischemia and infarction, rescue therapy, and safety were evaluated. RESULTS: The study was halted when a phase 3 study of intraventricular EG-1962 stopped because that study was unlikely to meet its primary endpoint. Six subjects were randomized (5 EG-1962 and 1 oral nimodipine). After 90-d follow-up, favorable outcome on the eGOS occurred in 1 of 5 EG-1962 and in the single oral nimodipine patient. Four EG-1962 and the oral nimodipine subject had angiographic vasospasm. One EG-1962 subject had delayed cerebral ischemia, and all subjects with angiographic vasospasm received rescue therapy except 1 EG-1962 patient. One subject treated with EG-1962 developed right internal carotid and middle cerebral artery narrowing 5 mo after placement of EG-1962, leading to occlusion and cerebral infarction. Pharmacokinetics showed similar plasma concentrations of nimodipine in both groups. CONCLUSION: Angiographic vasospasm and unfavorable clinical outcome still occurred after placement of EG-1962. Internal carotid artery narrowing and occlusion after placement of EG-1962 in the basal cisterns has not been reported.

Treatment of dural arteriovenous fistula using ethylene vinyl alcohol (onyx) arterial embolization as the primary modality: short-term results.

OBJECT: A dural arteriovenous fistula (DAVF) typically involves meningeal feeding arteries and can cause clinical symptoms ranging from tinnitus to rupture of draining cortical or parenchymal veins. Surgical treatment may be technically demanding. Ethylene vinyl alcohol (Onyx, ev3 Neurovascular) has several properties that make it potentially useful as a primary treatment agent for DAVF. Onyx is expected to be a permanent embolic agent. It should have a decreased risk of catheter retention when compared with other permanent embolic materials. METHODS: The authors report a series of six patients with symptomatic DAVF who were treated initially with transarterial Onyx embolization and other endovascular techniques. RESULTS: Five patients had complete occlusion of their DAVF noted on the follow-up angiogram obtained between 2 and 4 months. One patient had residual filling via a small arterial branch that was stable on follow-up angiography. None of the patients had worsening of neurological function. One case was complicated by a retained catheter fragment. CONCLUSIONS: Transarterial Onyx embolization and other endovascular methods can angiographically obliterate DAVF. In some cases, embolization allowed occlusion of multiple arterial feeding arteries from a single arterial injection. Technically, the embolization was optimized when a microcatheter position immediately adjacent to the point(s) of fistulization was achieved.

Use of a Polytetrafluoroethylene-Coated Vascular Plug for Focal Intracranial Parent Vessel Sacrifice for Fusiform Aneurysm Treatment.

BACKGROUND: Fusiform intracranial aneurysms are challenging due to the circumferential nature of the disease. Endovascular parent vessel sacrifice with coils may be a treatment option, but typically requires a long vessel segment to induce complete cessation of flow. OBJECTIVE: We evaluate early clinical experience with the intracranial use of the microvascular plug (MVP; Medtronic, Dublin, Ireland) device and to compare to previous coil-only techniques for vertebral artery sacrifice for fusiform vertebral aneurysm. METHODS: We reviewed patients treated with the MVP for intracranial aneurysms at our institution. As a case-control study, we located 6 control patients who underwent coiling alone for vertebral artery sacrifice. The number of implants, fluoroscopy time, and procedural charges were compared using unpaired t -tests. RESULTS: Twelve patients underwent vessel sacrifices with MVP. Eight were for vertebral artery dissecting aneurysms. Comparing only vertebral aneurysms, the mean implants was 7 in the MVP group (n = 8) and 19.5 in the coiling group (n = 6; P = .0015). Mean fluoroscopy time was 17.62 min in the MVP group compared to 24.2 min in the coiling group ( P = .07). Procedural costs were less in the MVP group ($19 667.38) compared to coiling ($44 909.50, P = .05). There were no technical failures and no cases with persistent flow in the parent vessel at the end of the procedure. CONCLUSION: The MVP is a cost-effective device for focal intracranial vessel occlusion in select patients. This is an important tool for cerebrovascular surgeons, particularly in cases of ruptured dissecting vertebral aneurysms.

Combined preoperative onyx embolization and protective internal carotid artery covered stent placement for treatment of glomus vagale tumor: review of literature and illustrative case.

OBJECTIVE: Surgical resection of complex glomus vagale tumors can be complicated by extensive blood loss and might require surgical sacrifice of an encased internal carotid artery. METHODS: A young patient presented with mass effect from glomus valage tumor. Computerized tomography angiography showed an encased internal carotid artery. Cerebral angiography demonstrated a highly vascular tumor. A literature review was performed for endovascular treatment options for neck tumors. RESULTS: Staged preoperative embolization of feeder arteries via internal maxillary artery, and thyrocervical trunk with onyx was performed. A covered stent was implanted in the cervical internal carotid artery to the common carotid artery; this resulted in complete devascularization of the tumor with exclusion of external carotid artery from the circulation. This is followed by surgical resection of the tumor. CONCLUSION: Preoperative embolization with onyx decreased the amount of blood loss intra-operatively. The implantation of a covered stent in the cervical internal carotid artery through the common carotid artery contributed for further devasculatization of the tumor bed, as well as provided a lumen continuity in case iatrogenic carotid injury is encountered intra-operatively.

Elastomer surfaces with directionally dependent adhesion strength and their use in transfer printing with continuous roll-to-roll applications.

In this paper we present mechanics and materials aspects of elastomeric stamps that have angled features of relief on their surfaces, designed to enable control of adhesion strength by peeling direction, in a way that can be exploited in schemes for deterministic assembly by transfer printing. Detailed mechanics models capture the essential physics of interface adhesion in this system. Experiments with cylindrical stamps that have this design demonstrate their potential for use in a continuous, roller mode of operation.