Neurocognitive Outcomes in a Cisternal Blood Injection Murine Model of Subarachnoid Hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) results in neurocognitive dysfunction and anxiety in humans and in animal models. Neurobehavioral tests such as the Morris Water Maze (MWM) and Elevated Plus Maze (EPM) tests are validated in several models of SAH but have not been tested in the murine cisternal blood injection SAH model. METHODS: Adult C57BL/6 mice (n=16) were randomized into two groups. Group 1 (n=8) received sham surgery. Group 2 (n=8) underwent SAH with 60 µL of autologous blood injected into the cisterna magna. Mice were then tested using the Modified Garcia Score on post-operative day 2 (POD2), EPM on POD5 & POD16, and MWM on POD6-16.Brain tissues harvested on POD16 were stained with Fluoro-Jade C to identify neurodegeneration in the hippocampus and cortex and Iba-1 immunofluorescence staining for microglial activation in the dentate gyrus and CA1 region of the hippocampus. RESULTS: SAH mice showed increased escape latency on POD10. Swim distance was significantly increased on POD9-10 and swim speed was significantly decreased on POD6&POD10 in SAH mice. SAH mice exhibited a trend for lowered proportion of covered arm entries in EPM on POD16. Modified Garcia Score was not significantly different between the groups on POD2. The area of microglial activation in the dentate gyrus and CA1 region of the hippocampus was mildly increased but not significantly different at day 16 after SAH. Similarly, no significant differences were noted in the number of Fluoro-Jade C (+) cells in cortex or hippocampus. CONCLUSIONS: Cisternal single blood injection in mice produces mild neurocognitive deficits most pronounced in spatial learning and most evident 10 days after SAH.

Comparative assessment of thermal injury induced by bipolar electrocautery systems in a porcine model.

BACKGROUND: Bipolar electrocautery systems used during neurosurgical procedures have been shown to induce thermal injury to surrounding tissue. The goal of this study was to compare the thermal injury induced by two different systems commonly used in neurosurgical procedures (Silverglide by Stryker Corporation and SpetzlerMalis by Codman Neuro), with that of a newly introduced device (TRIOwand by NICO Corporation). METHODS: A farm swine underwent craniectomy and durotomy with subsequent exposure of cortical brain tissue. Electrocoagulation for the duration of 3 s was conducted with three different bipolar systems under comparable power settings. The maximal depth of thermal injury and mean area of injury in Hematoxylin and Eosin stained slides were quantified using Image J. The tissues were evaluated for vacuolization and ischemic damage. One-way ANOVA followed by post hoc Tukey test was utilized for statistical analysis. Alpha level was set at 0.05. RESULTS: TRIOwand lesions showed less depth of injury when compared to both Spetzler-Malis (P < 0.001) and Silverglide lesions (P = 0.048). Silverglide lesions showed significantly less depth of injury when compared to SpetzlerMalis lesions (P < 0.001). The injury area induced by the TRIOwand was significantly less than that of Spetzler-Malis (P < 0.001) and Silverglide systems (P < 0.001). Ischemic changes and vacuolization were seen in all three groups. CONCLUSION: Thermal damage is induced to varying extents by all bipolar systems. In this porcine model and under the conditions tested, bipolar cauterization with the TRIOwand resulted in less depth and decreased mean area of injury. Further studies are needed to characterize the injury caused by different bipolar systems with other settings and under surgical conditions in humans.

Stroke-Induced Peripheral Immune Dysfunction in Vitamin D-Deficient Conditions: Modulation by Progesterone and Vitamin D.

Vitamin D deficiency (Ddef) alters morphology and outcomes after a stroke. We investigated the interaction of Ddef following post-stroke systemic inflammation and evaluated whether administration of progesterone (P) or vitamin D (D) will improve outcomes. Ddef rats underwent stroke with lipopolysaccharide (LPS)-induced systemic inflammation. Rats were randomly divided into 9 groups and treated with P, D, or vehicle for 4 days. At day 4, rats were tested on different behavioral parameters. Markers of neuronal inflammation, endoplasmic reticulum stress, oxidative stress, white matter integrity, and apoptosis were measured along with immune cell populations from the spleen, thymus, and blood. Severely altered outcomes were observed in the Ddef group compared to the D-sufficient (Dsuf) group. Stroke caused peripheral immune dysfunction in the Dsuf group which was worse in the Ddef group. Systemic inflammation exacerbated injury outcomes in the Dsuf group and these were worse in the Ddef group. Monotherapy with P/D showed beneficial functional effects but the combined treatment showed better outcomes than either alone. Ddef as a comorbid condition with stroke worsens stroke outcomes and can delay functional recovery. Combination treatment with P and D might be promising for future stroke therapeutics in Ddef.

Vitamin D deficiency increases blood-brain barrier dysfunction after ischemic stroke in male rats.

Because vitamin D hormone deficiency (VDHdef) can worsen severity and outcome for ischemic stroke, we examined the role of VDH in maintaining blood-brain-barrier (BBB integrity) in a rat model of stroke. In most types of stroke, the BBB is markedly compromised, potentially leading to a cascade of injury processes and functional deficits, so we examined a number of biomarkers associated with BBB disruption to determine whether VDH deficiency would further compromise the BBB following a stroke. Male Wistar rats were randomly assigned to one of two diet cohorts, VDH-sufficient (VDHsuf) and VDHdef. The VDHsuf group was fed standard rat chow and the VDHdef group got a VDH-null version of the same diet for 8 weeks. Animals from both cohorts were subjected to transient middle cerebral artery occlusion (tMCAO) surgery, killed at 72 h post-stroke, and their brains evaluated for BBB permeability and injury severity using expression of immunoglobulin (IgG), matrix metalloproteinase-9 (MMP-9) activity and alteration of tight junction (TJ) proteins as markers of BBB disruption. We also evaluated modulation of glucose transporter-1 (GLUT1), osteopontin (OPN), ß-catenin and vitamin D receptor (VDR) expression in VDHsuf and VDHdef subjects. At the time of MCAO, rats on the VDHdef diet had circulating VDH levels one-fourth that of rats fed control chow. IgG extravasation after MCAO, indicating more severe BBB injury, was significantly higher in the MCAO+VDHdef than the MCAO+VDHsuf rats. Following MCAO, expression of MMP-9, GLUT1, VDR and OPN increased and the TJ proteins occludin and claudin-5 decreased significantly in the VDHdef compared to the VDHsuf group. We also observed significantly lower expression of ß-catenin in the MCAO group of both VDHsuf and VDHdef rats. Under these conditions, VDH deficiency itself can compromise the BBB. We think that low serum VDH levels are likely to complicate stroke severity and its chronic consequences.

The role of inflammation and potential use of sex steroids in intracranial aneurysms and subarachnoid hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) continues to be a devastating neurological condition with a high risk of associated morbidity and mortality. Inflammation has been shown to increase the risk of complications associated with aSAH such as vasospasm and brain injury in animal models and humans. The goal of this review is to discuss the inflammatory mechanisms of aneurysm formation, rupture and vasospasm and explore the role of sex hormones in the inflammatory response to aSAH. METHODS: A literature review was performed using PubMed using the following search terms: "intracranial aneurysm," "cerebral aneurysm," "dihydroepiandrosterone sulfate" "estrogen," "hormone replacement therapy," "inflammation," "oral contraceptive," "progesterone," "sex steroids," "sex hormones" "subarachnoid hemorrhage," "testosterone." Only studies published in English language were included in the review. RESULTS: Studies have shown that administration of sex hormones such as progesterone and estrogen at early stages in the inflammatory cascade can lower the risk and magnitude of subsequent complications. The exact mechanism by which these hormones act on the brain, as well as their role in the inflammatory cascade is not fully understood. Moreover, conflicting results have been published on the effect of hormone replacement therapy in humans. This review will scrutinize the variations in these studies to provide a more detailed understanding of sex hormones as potential therapeutic agents for intracranial aneurysms and aSAH. CONCLUSION: Inflammation may play a role in the pathogenesis of intracranial aneurysm formation and subarachnoid hemorrhage, and administration of sex hormones as anti-inflammatory agents has been associated with improved functional outcome in experimental models. Further studies are needed to determine the therapeutic role of these hormones in the intracranial aneurysms and aSAH.

Current Perspectives in Imaging Modalities for the Assessment of Unruptured Intracranial Aneurysms: A Comparative Analysis and Review.

BACKGROUND: Intracranial aneurysms (IAs) are pathologic dilatations of cerebral arteries. This systematic review summarizes and compares imaging techniques for assessing unruptured IAs (UIAs). This review also addresses their uses in different scopes of practice. Pathophysiologic mechanisms are reviewed to better understand the clinical usefulness of each imaging modality. METHODS: A literature review was performed using PubMed with these search terms: "intracranial aneurysm," "cerebral aneurysm," "magnetic resonance angiography (MRA)," computed tomography angiography (CTA)," "catheter angiography," "digital subtraction angiography," "molecular imaging," "ferumoxytol," and "myeloperoxidase". Only studies in English were cited. RESULTS: Since the development and improvement of noninvasive diagnostic imaging (computed tomography angiography and magnetic resonance angiography), many prospective studies and meta-analyses have compared these tests with gold standard digital subtraction angiography (DSA). Although computed tomography angiography and magnetic resonance angiography have lower detection rates for UIAs, they are vital in the treatment and follow-up of UIAs. The reduction in ionizing radiation and lack of endovascular instrumentation with these modalities provide benefits compared with DSA. Novel molecular imaging techniques to detect inflammation within the aneurysmal wall with the goal of stratifying risk based on level of inflammation are under investigation. CONCLUSIONS: DSA remains the gold standard for preoperative planning and follow-up for patients with IA. Newer imaging modalities such as ferumoxytol-enhanced magnetic resonance imaging are emerging techniques that provide critical in vivo information about the inflammatory milieu within aneurysm walls. With further study, these techniques may provide aneurysm rupture risk and prediction models for individualized patient care.

Effect of Progesterone on Cerebral Vasospasm and Neurobehavioral Outcomes in a Rodent Model of Subarachnoid Hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) induces widespread inflammation leading to cellular injury, vasospasm, and ischemia. Evidence suggests that progesterone (PROG) can improve functional recovery in acute brain injury owing to its anti-inflammatory and neuroprotective properties, which could also be beneficial in SAH. We hypothesized that PROG treatment attenuates inflammation-mediated cerebral vasospasm and microglial activation, improves synaptic connectivity, and ameliorates functional recovery after SAH. METHODS: We investigated the effect of PROG in a cisternal SAH model in adult male C57BL/6 mice. Neurobehavioral outcomes were evaluated using rotarod latency and grip strength tests. Basilar artery perimeter, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor 1 (GluR1)/synaptophysin colocalization, and Iba-1 immunoreactivity were quantified histologically. RESULTS: PROG (8 mg/kg) significantly improved rotarod latency at day 6 and grip strength at day 9. PROG-treated mice had significantly reduced basilar artery vasospasm at 24 hours. GluR1/synaptophysin colocalization, indicative of synaptic GluR1, was significantly reduced in the SAH+Vehicle group at 24 hours, and PROG treatment significantly attenuated this reduction. PROG treatment significantly reduced microglial cell activation and proliferation in cerebellum and cortex but not in the brainstem at 10 days. CONCLUSIONS: PROG treatment ameliorated cerebral vasospasm, reduced microglial activation, restored synaptic GluR1 localization, and improved neurobehavioral performance in a murine model of SAH. These results provide a rationale for further translational testing of PROG therapy in SAH.

Nontraumatic, posterior circulation pseudoaneurysm of the basilar artery summit with complete spontaneous resolution: Case report and literature review.

BACKGROUND: Intracranial pseudoaneurysms are rare vascular defects of arterial walls that are classically the result of traumatic injury, iatrogenic causes, or infection. Idiopathic pseudoaneurysms are seen even less frequently and are often related to atherosclerosis. Pseudoaneurysms are most commonly found along the distal wall of the internal carotid artery, however, can occur at any location in the cerebrovascular circulation. Treatment of these arterial defects is often challenging due to their frail nature. CASE DESCRIPTION: A 61-year-old male with a history of hypertension presented with a severe, atypical headache without history of trauma. Computed tomography (CT) and computed tomography angiography (CTA) demonstrated diffuse subarachnoid hemorrhage. Imaging demonstrated a 3.5 mm pseudoaneurysm projecting distally from the basilar artery at the apex. Repeated imaging (CTA, digital subtraction angiography) demonstrated decreased size and flow associated within the aneurysm over the following 2 weeks; as such, the patient was managed conservatively. The patient was discharged in neurologically intact condition when imaging at 14 days confirmed complete and spontaneous resolution of the pseudoaneurysm. CONCLUSION: Idiopathic pseudoaneurysms that are commonly associated with atherosclerosis are most commonly managed surgically or endovascularly. Conservative approach may be considered in a select group of patients that exhibit decreased size and/or flow within the aneurysm in repeated imaging; spontaneous resolution was seen in the present case.

Progesterone modulates diabetes/hyperglycemia-induced changes in the central nervous system and sciatic nerve.

We investigated the effect of progesterone (P4) treatment on diabetes/hyperglycemia-induced pathological changes in brain, spinal cord and sciatic nerve tissue in male rats. Animals were rendered hyperglycemic by a single dose of streptozotocin (STZ). P4 treatment was started after hyperglycemia was confirmed and body weight and blood glucose levels were monitored once/week for 5weeks. Rats underwent behavioral testing at week 5 and were then euthanized for histology. We assessed the expression of markers of angiogenesis (vascular endothelial growth factor (VEGF)), inflammation (interleukin-6 (IL-6)) and tissue injury (CD11b, NG2, COX2 and matrix metalloproteinase-2 (MMP-2)) in the brain, spinal cord and sciatic nerve. We also examined the regenerative effect of P4 on pathological changes in intra-epidermal nerve fibers (IENF) of the footpads. Diabetes/hyperglycemia led to body weight loss over 5weeks and P4 treatment reduced this loss. At week 5, blood-glucose levels were significantly lower in the P4-treated diabetic group compared to vehicle. Compared to sham or P4-treated groups, the diabetic vehicle group showed hyperactivity on the spontaneous locomotor activity test. Western blot data revealed upregulation of VEGF, IL-6, CD11b, NG2, COX2 and MMP-2 levels in the vehicle group and P4 treatment normalized these expression levels. IENF densities were reduced in the vehicle group and normalized after P4 treatment. We conclude that P4 can reduce some of the chronic pathological responses to STZ-induced diabetes.

Neurobehavioral testing in subarachnoid hemorrhage: A review of methods and current findings in rodents.

The most important aspect of a preclinical study seeking to develop a novel therapy for neurological diseases is whether the therapy produces any clinically relevant functional recovery. For this purpose, neurobehavioral tests are commonly used to evaluate the neuroprotective efficacy of treatments in a wide array of cerebrovascular diseases and neurotrauma. Their use, however, has been limited in experimental subarachnoid hemorrhage studies. After several randomized, double-blinded, controlled clinical trials repeatedly failed to produce a benefit in functional outcome despite some improvement in angiographic vasospasm, more rigorous methods of neurobehavioral testing became critical to provide a more comprehensive evaluation of the functional efficacy of proposed treatments. While several subarachnoid hemorrhage studies have incorporated an array of neurobehavioral assays, a standardized methodology has not been agreed upon. Here, we review neurobehavioral tests for rodents and their potential application to subarachnoid hemorrhage studies. Developing a standardized neurobehavioral testing regimen in rodent studies of subarachnoid hemorrhage would allow for better comparison of results between laboratories and a better prediction of what interventions would produce functional benefits in humans.

External ventricular drain practice variations: results from a nationwide survey.

OBJECTIVE While guidelines exist for many neurosurgical procedures, external ventricular drain (EVD) insertion has yet to be standardized. The goal of this study was to survey the neurosurgical community and determine the most frequent EVD insertion practices. The hypothesis was that there would be no standard practices identified for EVD insertion or methods to avoid EVD-associated infections. METHODS The American Association of Neurological Surgeons membership database was queried for all eligible neurosurgeons. A 16-question, multiple-choice format survey was created and sent to 7217 recipients. The responses were collected electronically, and the descriptive results were tabulated. Data were analyzed using the chi-square test. RESULTS In total, 1143 respondents (15.8%) completed the survey, and 705 respondents (61.6%) reported tracking EVD infections at their institution. The most common self-reported infection rate ranged from 1% to 3% (56.1% of participants), and 19.7% of respondents reported a 0% infection rate. In total, 451 respondents (42.7%) indicated that their institution utilizes a formal protocol for EVD placement. If a respondent's institution had a protocol, only 258 respondents (36.1%) always complied with the protocol. Protocol utilization for EVD insertion was significantly more frequent among residents, in academic/hybrid centers, in ICU settings, and if the institution tracked EVD-associated infection rates (p < 0.05). A self-reported 0% infection rate was significantly more commonly associated with a higher level of training (e.g., attending physicians), private center settings, a clinician performing 6 to 10 EVD insertions within the previous 12 months, and prophylactic continuous antibiotic utilization (p < 0.05). CONCLUSIONS This survey demonstrated heterogeneity in the practices for EVD insertion. No standard practices have been proposed or adopted by the neurosurgical community for EVD insertion or complication avoidance. These results highlight the need for the nationwide standardization of technique and complication prevention measures.

Adult Intramedullary Teratoma of the Spinal Cord: A Case Report and Review of Literature.

BACKGROUND: Teratomas of the spinal cord constitute 0.1% of all spinal tumors, and these lesions are extremely rare in adults. The authors describe a rare case of intradural intramedullary teratoma of the conus medullaris and perform review of literature of intramedullary teratomas seen in the thoracolumbar region. CASE DESCRIPTION: A 48-year-old man presented with fasciculations in the bilateral upper and lower extremities. Radiologic findings revealed an L2-L3 level intradural, nonenhancing, extramedullary cystic mass measuring 15 × 13 mm with a 6-mm enhancing nodule at the level of the conus medullaris. The patient was followed up for 1 year, during which time enlargement of the lesion with new areas of patchy contrast enhancement were observed. L1-L2 decompressive laminectomies were performed, and gross total resection of the lesion was achieved. Histopathologic examination confirmed the diagnosis of benign mature cystic teratoma. A literature review revealed no incidence difference in intramedullary teratomas between males and females (P > 0.05). The mean age at the time of diagnosis was 36.4 ± 12.3 years for men and 41.3 ± 11.6 for women (P < 0.05). The mean symptom duration before treatment was 64.6 ± 79.4 months for females and 20.7 ± 13.8 months for men (P < 0.05). Complete resection was achieved in 48.1% of the cases. CONCLUSIONS: Teratomas should be taken into consideration in the differential diagnosis of intramedullary lesions when the imaging reveals variable signal intensity because of tissue heterogeneity. A partial resection is a viable treatment option when the lesion is attached to vital structures because of the low recurrence rates reported in the literature.

Sex Differences in the Formation of Intracranial Aneurysms and Incidence and Outcome of Subarachnoid Hemorrhage: Review of Experimental and Human Studies.

Intracranial aneurysms are defined as pathological dilatations of cerebral arteries and rupture of intracranial aneurysms leads to subarachnoid hemorrhage (SAH). The goal of this review was to outline the sex differences in the formation and progression of intracranial aneurysms as well as sex-related differences in incidence and outcome of SAH. The literature review was performed using PubMed with a combination of these search terms: "subarachnoid hemorrhage," "incidence," "outcome," "sex," "gender," "male," "female," "experimental," "mice," and "rats." Studies written in English were used. Female sex is thought to be a risk factor for aneurysm formation, especially in postmenopausal age populations, suggesting the potential protective involvement of sex steroids. Female sex is also considered a risk factor for SAH occurrence. Although incidence and mortality are confirmed to be higher in females in most studies, they elucidated no clear differences in the functional outcome among SAH survivors. The effect of gender on the pathophysiology of SAH is not very well understood; nevertheless, the majority of pre-clinical studies suggest a beneficial effect of sex steroids in experimental SAH. Moreover, conflicting results exist on the role and effect of hormone replacement therapies and oral contraceptive pills on the incidence and outcome of human SAH. Sex differences exist in the formation of aneurysms as well as the incidence and mortality of SAH. Potential therapeutic effects of sex steroids have been replicated in many animal studies, but their potential use in the treatment of acute SAH in human populations needs more future study.

Upper Nasopharyngeal Corridor for Transnasal Endoscopic Drainage of Petroclival Cholesterol Granulomas: Alternative Access in Conchal Sphenoid Patients.

Background Cholesterol granulomas arising at the petrous apex can be treated via traditional open surgical, endoscopic, and endoscopic-assisted approaches. Endoscopic approaches require access to the sphenoid sinus, which is technically challenging in patients with conchal sphenoidal anatomy. Clinical Presentation A 55-year-old woman presented with intermittent headaches and tinnitus. Formal audiometry demonstrated moderately severe bilateral hearing loss. CT of the temporal bones and sella revealed a well-demarcated expansile lytic mass. MRI of the face, orbit, and neck showed a right petrous apex mass measuring 22 × 18 × 19 mm that was hyperintense on T1- and T2-weighted images without enhancement, consistent with a cholesterol granuloma. The patient had a conchal sphenoidal anatomy. Operative Technique Herein, we present an illustrative case of a low-lying petroclival cholesterol granuloma in a patient with conchal sphenoidal anatomy to describe an alternative high nasopharyngeal corridor for endoscopic transnasal transclival access. Postoperative Course Postoperatively, the patient's symptoms recovered and no complications occurred. Follow-up imaging demonstrated a patent drainage tract without evidence of recurrence. Conclusion In patients with a conchal sphenoid sinus, endoscopic transnasal transclival access can be gained using a high nasopharyngeal approach. This corridor facilitates safe access to these lesions and others in this location.

Intracranial dural arteriovenous fistula as a cause for symptomatic superficial siderosis: A report of two cases and review of the literature.

BACKGROUND: Superficial siderosis (SS) is the occult deposition of hemosiderin within the cerebral cortex due to repeat microhemorrhages within the central nervous system. The collection of hemosiderin within the pia and superficial cortical surface can lead to injury to the nervous tissue. The most common presentation is occult sensorineural hearing loss although many patients have been misdiagnosed with diseases such as multiple sclerosis and amyotrophic lateral sclerosis before being diagnosed with SS. Only one case report exists in the literature describing an intracranial dural arteriovenous fistula (dAVF) as the putative cause for SS. CASE DESCRIPTION: We describe two cases of SS caused by a dAVF. Both patients had a supratentorial, cortical lesion supplied by the middle meningeal artery with venous drainage into the superior sagittal sinus. In both patients, symptoms improved after endovascular embolization. The similar anatomic relationship of both dAVFs reported presents an interesting question about the pathogenesis of SS. Similar to the pathologic changes seen in the formation of intracranial arterial aneurysms; it would be possible that changes in the blood vessel lining and wall might predispose a patient to chronic, microhemorrhage resulting in SS. CONCLUSIONS: We describe the second and third cases of a dAVF as the cause of SS, and the first cases of successful treatment of SS-associated dAVF with endovascular embolization. As noninvasive imaging techniques become more sensitive and easily obtained, one must consider their limitations in detecting occult intracranial vascular malformations such as dAVF as a possible etiology for SS.

Evaluating the neurotherapeutic potential of a water-soluble progesterone analog after traumatic brain injury in rats.

The poor aqueous solubility of progesterone (PROG) limits its potential use as a therapeutic agent. We designed and tested EIDD-1723, a novel water-soluble analog of PROG with >100-fold higher solubility than that of native PROG, as candidate for development as a field-ready treatment for traumatic brain injury (TBI). The pharmacokinetic effects of EIDD-1723 on morphological and functional outcomes in rats with bilateral cortical impact injury were evaluated. Following TBI, 10-mg/kg doses of EIDD-1723 or PROG were given intramuscularly (i.m.) at 1, 6 and 24 h post-injury, then daily for the next 6 days, with tapering of the last 2 treatments. Rats were tested pre-injury to establish baseline performance on grip strength and sensory neglect, and then retested at 4, 9 and 21 days post-TBI. Spatial learning was evaluated from days 11-17 post-TBI. At 22 days post-injury, rats were perfused and brains extracted and processed for lesion size. For the edema assay the animals were killed and brains removed at 24 h post-injury. EIDD-1723 significantly reduced cerebral edema and improved recovery from motor, sensory and spatial learning deficits as well as, or better than, native PROG. Pharmacokinetic investigation after a single i.m. injection in rats revealed that EIDD-1723 was rapidly converted to the active metabolite EIDD-036, demonstrating first-order elimination kinetics and ability to cross the blood-brain barrier. Our results suggest that EIDD-1723 represents a substantial advantage over current PROG formulations because it overcomes storage, formulation and delivery limitations of PROG and can thereby reduce the time between injury and treatment.

Resolution of Oculomotor Nerve Palsy Secondary to Posterior Communicating Artery Aneurysms: Comparison of Clipping and Coiling.

BACKGROUND: Previous studies have attempted to determine the best treatment for oculomotor nerve palsy (ONP) secondary to posterior communicating artery (PCoA) aneurysms, but have been limited by small sample sizes and limited treatment. OBJECTIVE: To analyze the treatment of ONP secondary to PCoA with both coiling and clipping in ruptured and unruptured aneurysms. METHODS: Data from 2 large academic centers was retrospectively collected over 22 years, yielding a total of 93 patients with ONP secondary to PCoA aneurysms. These patients were combined with 321 patients from the literature review for large data analyses. Onset symptoms, recovery, and time to resolution were evaluated with respect to treatment and aneurysm rupture status. RESULTS: For all patients presenting with ONP (n = 414) 56.6% of those treated with microsurgical clipping made a full recovery vs 41.5% of those treated with endovascular coil embolization (P = .02). Of patients with a complete ONP (n = 229), full recovery occurred in 47.3% of those treated with clipping but in only 20% of those undergoing coiling (P = .01). For patients presenting with ruptured aneurysms (n = 130), full recovery occurred in 70.9% compared with 49.3% coiled patients (P = .01). Additionally, although patients with full ONP recovery had a median time to treatment of 4 days, those without full ONP recovery had a median time to treatment of 7 days (P = .01). CONCLUSION: Patients with ONP secondary to PCoA aneurysms treated with clipping showed higher rates of full ONP resolution than patients treated with coil embolization. Larger prospective studies are needed to determine the true potential of recovery associated with each treatment. ABBREVIATIONS: EUH, Emory University HospitalIQR, interquartile rangeJHU, Johns Hopkins UniversitymRS, modified Rankin ScaleONP, oculomotor nerve palsyPCoA, posterior communicating arterySAH, subarachnoid hemorrhage.

Inflammation, vasospasm, and brain injury after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) can lead to devastating neurological outcomes, and there are few pharmacologic treatments available for treating this condition. Both animal and human studies provide evidence of inflammation being a driving force behind the pathology of SAH, leading to both direct brain injury and vasospasm, which in turn leads to ischemic brain injury. Several inflammatory mediators that are elevated after SAH have been studied in detail. While there is promising data indicating that blocking these factors might benefit patients after SAH, there has been little success in clinical trials. One of the key factors that complicates clinical trials of SAH is the variability of the initial injury and subsequent inflammatory response. It is likely that both genetic and environmental factors contribute to the variability of patients' post-SAH inflammatory response and that this confounds trials of anti-inflammatory therapies. Additionally, systemic inflammation from other conditions that affect patients with SAH could contribute to brain injury and vasospasm after SAH. Continuing work on biomarkers of inflammation after SAH may lead to development of patient-specific anti-inflammatory therapies to improve outcome after SAH.