Visualization of both proximal M2-MCA segments in patients (the Tilted-V Sign) with acute M1-MCA occlusion stroke is associated with better procedural and prognostic outcomes.

Introduction: We aimed to assess the clinical significance of M1-MCA occlusion with visualization of both MCA-M2 segments ["Tilted-V sign" (TVS)] on initial CT angiography (CTA) in patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy (EVT). Methods: Data for patients with consecutive AIS undergoing EVT for large vessel occlusion (LVO) in two academic centers are recorded in ongoing databases. Patients who underwent EVT for M1-MCA occlusions ≤ 6 h from symptom onset were included in this retrospective analysis. Results: A total of 346 patients met the inclusion criteria; 189 (55%) had positive TVS. Patients with positive TVS were younger (68 ± 14 vs. 71 ± 14 years, P = 0.028), with similar rates of vascular risk factors and baseline modified Rankin scores (mRS) 0-2. The rates of achieving thrombolysis in cerebral ischemia (TICI) 2b-3 were similar to the two groups (79%), although successful first-pass recanalization was more common with TVS (64 vs. 36%, p = 0.01). On multivariate analysis, higher collateral score [odds ratio (OR) 1.38 per unit increase, p = 0.008] and lower age (OR 0.98 per year increase, p = 0.046) were significant predictors of TVS. Patients with positive TVS had higher post-procedural Alberta Stroke Program Early CT Score (ASPECTS; 6.9 ± 2.2 vs. 5.2 ± 2.3, p = 0.001), were discharged with lower National Institutes of Health Stroke Score (NIHSS; 6±6 vs. 9±7, p = 0.003) and higher rates of mRS 0-2 (29.5 vs. 12%, p = 0.001), and had lower rates of 90-day mortality (13.2 vs. 21.6%, p = 0.038). However, TVS was not an independent predictor of functional independence (OR 2.51; 95% CI 0.7-8.3). Conclusion: Tilted-V Sign, an easily identifiable radiological marker, is associated with fewer recanalization attempts, better functional outcomes, and reduced mortality.

Minimally Invasive Subtemporal Intradural Approach for Penetrating Orbitocranial Injury by Wooden Foreign Body Into the Lateral Wall of the Cavernous Sinus.

Non-missile transorbital penetrating head injuries are relatively rare, though potentially fatal injuries. Trajectory for intracranial entrance is typically via the orbital roof, the superior orbital fissure (SOF), or the optic canal. Non-metallic intracranial penetrating injuries are even scarcer and may pose unusual diagnostic and surgical challenges. Here we present and discuss a unique case of a penetrating injury by a wooden foreign body (FB) which entered and expanded the inter-dural space of the lateral cavernous sinus (CS) sinus wall without intracavernous or intradural involvement. The patient was a 71 year-old male who fell face-down and sustained a penetrating transorbital injury by a dry twig fragment, which passed through the SOF and into the interdural space of lateral wall of the ipsilateral CS. The patient was fully conscious (GCS15) at presentation but had severe ocular injury (complete ophthalmoplegia and blindness of the injured eye). The wooden FB was successfully removed via a minimally invasive subtemporal intradural approach with no apparent immediate or long-term complications. We emphasize the unusual diagnostic and surgical challenges related to this kind of rare injuries as reflected by the decision-making considerations taken in the presented case.

The Chiasmal Compression Index: An Integrative Assessment Tool for Visual Disturbances in Patients with Pituitary Macroadenomas.

OBJECTIVE: Visual status is routinely evaluated by neuro-ophthalmologic examination and computerized visual field (VF) tests in patients with chiasmal compression secondary to pituitary macroadenoma. Currently, no relevant data exists to accurately quantify the extent of optic apparatus compromise to further guide clinical decision-making. We aimed to assess for a possible quantitative correlation between optic chiasm geometric properties on magnetic resonance imaging (MRI) and VF deficits. METHODS: Visual assessments and concurrent MRI scans were retrospectively reviewed from patients treated for pituitary macroadenoma in a single medical institution. Chiasm width, chiasm minimal and maximal height, and chiasm angle were measured on MRI coronal plane images by 3 independent reviewers (for the sake of variability analysis). VF numerical summary parameters were also retrieved. RESULTS: A total of 30 patients were included in the final analysis. Average VF index was 70% (±30), and averaged mean deviation was 10.0 db (±9). Chiasm angle and width (which together represents the bending and stretching of the chiasm by the upward directed compression; both of which demonstrated high inter- and intraobserver agreement) showed strong correlation with VF loss. Chiasmal compression index derived from those parameters showed even stronger correlation. CONCLUSIONS: The strong correlation demonstrated by our results of this relatively simple radiologic measurement with VF status, despite the relatively small cohort, calls for further investigation in this promising direction, and may facilitate with basic assessment and clinical decision-making for patients with equivocal neuro-ophthalmologic evaluation, as well as with poor compliance.

Unfavorable functional outcome is expected for elderly patients suffering from acute subdural hematoma even when presenting with preserved level of consciousness.

Alongside an increase in life expectancy, median age of patients presenting with traumatic acute subdural hematomas (ASDH) has increased as well. Treatment guidelines are based on studies performed on relatively young patients. The optimal management of elderly (>70 years old) patients with ASDH, specifically those with relatively preserved level of consciousness, was not thoroughly investigated so far. We retrospectively examined elderly patients presented to our medical center between the years 2006-2016 with traumatic convexity ASDH and GCS of 13-15. 773 patients were included in the initial cohort and 54 patients were included in the final analysis. The mean age at presentation was 81.5 years and the means of hematoma thickness and midline shift were 15.5 mm and 6.6 mm, respectively. Patients in our cohort had an overall unfavorable outcome (mRS 5-6) of 28% and 56% at discharge and at 1 year following injury, respectively. The results were not significantly different for the subgroups of patients older than 80 years and patients with high ASA-PS. Surgical evacuation of the ASDH was undertaken in 28 patients with focal neurologic deficit and/or worsening on subsequent brain scans. At 1 year, 64% (18 patients) in the surgery group had unfavorable outcome compared to 48% (12 patients) in the conservative group. We believe that these numbers should be taken under consideration when assessing elderly patients with convexity ASDH and relatively preserved level of consciousness.

INTRAMEDULLARY SPINAL CORD METASTASIS AS THE PRESENTING FEATURE OF PAPILLARY THYROID CARCINOMA.

OBJECTIVE: The objective of this report is to present an unusual case of intramedullary spinal cord metastasis (ISCM) as the presenting feature of papillary thyroid carcinoma (PTC). METHODS: The presented case includes clinical, biochemical, and imaging findings as well as surgical and pathology reports. Treatment with radioactive iodine (RAI) and the response to this treatment are presented. RESULTS: A 71-year-old woman was evaluated for debilitating low back pain and walking disability. Magnetic resonance imaging demonstrated an oval, lumbar, intramedullary mass with benign features and surgery was scheduled. On preoperative evaluation for the lumbar mass, a multinodular thyroid goiter (unfortunately overlooked previously) was noticed, causing severe narrowing of the trachea. Total thyroidectomy was performed with a pathology diagnosis of PTC. In a second operation, the lumbar lesion was removed and proved to represent metastatic PTC. External beam radiation was subsequently administered to the thyroid bed, lumbar spine, and other skeletal metastases, followed by 150 milliCurie of RAI. A post-treatment scan showed high uptake over the lumbar spine, and skeletal and lung lesions. Clinically, the patient restored her walking ability and back pain improved. CONCLUSION: ISCM rarely is the presenting feature of PTC. Our patient presented with back pain which is the typical, though non-specific symptom, of ISCM. She showed good clinical response to multimodal treatment which is in line with the few other differentiated thyroid cancer patients with ISCM reported in the literature. Prompt surgical resection, followed by external beam radiation and RAI, may improve neurological signs, alleviate pain, and improve quality of life.

Ovarian hyperstimulation syndrome leading to ventriculoperitoneal shunt malfunction: Case report.

Ventriculoperitoneal shunt (VPS) insertion is a common neurosurgical procedure for hydrocephalus. Unfortunately, VPS malfunction is not uncommon, with an estimated cumulative rate of 32% at 5 years. As flow through the shunt is influenced by the pressure gradient between the ventricles and the peritoneal cavity, malfunction may be caused by elevated intra-abdominal pressure. We present a rare patient with ascites following ovarian hyperstimulation syndrome (OHSS) leading to shunt malfunction. OHSS is a potentially life-threatening complication of controlled ovarian stimulation caused by the administration of exogenous gonadotropins. In this patient clinical and radiological resolution of shunt dysfunction were achieved following peritoneocentesis. To our knowledge this is the first described case of OHSS leading to shunt malfunction, emphasizing the importance of awareness, early recognition and proper management of abdominal etiologies of VPS malfunction.

Assessment of Optic Pathway Structure and Function in Patients With Compression of the Optic Chiasm: A Correlation With Optical Coherence Tomography.

PURPOSE: The purpose of this study was to investigate correlations between retinal fiber thickness measured by optical coherence tomography (OCT) and anterograde functional and structural differences in the optic pathway of patients with compression of the optic chiasm. Our hypothesis was that loss of visual acuity caused by chronic compressive pathologies may lead to an irreversible decline in vision because of permanent neurodegeneration of the optic radiations and visual cortex. METHODS: Quantitative OCT, functional magnetic resonance imaging (MRI) and diffusion tensor MRI measurements were made in 17 patients being surgically treated for chiasmal compression. RESULTS: In our study we found that surgically irreversible visual field defects and reduced retinal nerve fiber layer thickness were significantly associated with lower fractional diffusion anisotropy and higher diffusivities in optic radiations and less functional MRI activation in the visual cortex. CONCLUSIONS: Damage to the retinal nerve fiber layer is associated with downstream structural and functional degradation of the optic pathway. This may be related to trans-synaptic degeneration and the fact that these factors are important potential imaging biomarkers for predicting visual recovery after surgical decompression.

Review of controversies in management of non-benign meningioma.

Meningiomas are one of the most common brain tumors. World Health Organisation (WHO) Grade II and Grade III meningiomas are grouped together as non-benign meningioma (NBM). There are several controversies surrounding NBM management, including the significance of extent of resection and the efficacy of post-operative radiation and drug treatment. We reviewed the literature to develop recommendations for management of NBM. The questions we sought to answer were: Does gross total resection (GTR) improve patient outcome? Is radiation therapy (RT) warranted after complete or after incomplete resection of NBM? What drug therapies have been proven to improve outcome in patients with NBM? We found that GTR improves outcome in WHO Grade II meningioma, and should be attempted whenever considered safe. GTR correlates less closely to outcome in Grade III meningioma compared to subtotal resection (STR). Extreme measures to completely resect Grade III meningioma are not warranted. RT following GTR of Grade II meningioma does not improve patient outcome, and may be reserved for recurrence. RT improves outcome following STR of Grade II meningioma. RT improves outcome after resection of Grade III meningioma. No drug therapy has been shown to improve outcome in NBM. This review elucidates recommendations for some of the controversies involving NBM.

Is a wake-up call in order? Review of the evidence for awake craniotomy.

Awake craniotomy (AC) has been used in increasing frequency in the past few decades. It has mainly been used for resection of intrinsic tumors, but also, rarely, for other pathologies. The vast majority of reports specific to one pathology, however, have focused on resection of low grade glioma in the awake setting. Tumors in eloquent areas have mainly been resected when the patient is awake for the purpose of preservation of function. Motor function is the most documented, and most successfully preserved function. Other functions are harder to localize with direct electrical stimulation (DES), and thus more difficult to preserve. The success rate of DES localization correlates to the rate of function preservation. The effect of AC on extent of resection is inconsistent in the literature. Other functions, such as sensory and visuospatial recognition, have been protected during AC, but this is best performed in large, referral centers that have experience with the procedure. Other benefits to AC, such as cost-effectiveness and reduction in patient pain and anxiety, have also been reported.

Ketamine delays mortality in an experimental model of hemorrhagic shock and subsequent sepsis.

BACKGROUND: In previous studies ketamine was reported to improve survival and decrease serum interleukin-6 (IL-6) concentration after sepsis alone and after burn injury followed by sepsis. The aim of this study was to determine whether ketamine alters survival and/or IL-6 after hemorrhagic shock alone or hemorrhagic shock followed by sepsis. MATERIALS AND METHODS: Rats were subjected to hemorrhagic shock with or without subsequent Gram-negative bacterial sepsis and were either treated with ketamine 5 mg/kg or were not treated. Blood was sampled for IL-6 determination prior to hemorrhage, at the completion of resuscitation, and at 6 and 30 h later. Mortality was recorded for 7 days following hemorrhage or hemorrhage+sepsis. RESULTS: After hemorrhage+sepsis the time to median mortality was significantly later in the ketamine-treated group (36 h) than in the control group (12 h). At 12h the survival rate of the ketamine-treated group (100%) was significantly higher than in the control group (55%). There were no significant differences between groups with respect to IL-6 or 7-day survival after either hemorrhage+sepsis or hemorrhage alone. CONCLUSION: Ketamine improved 12h survival and delayed mortality after hemorrhage+sepsis without significantly altering IL-6, and did not alter survival or IL-6 after hemorrhage alone.

Anti-inflammatory preconditioning by agonists of adenosine A1 receptor.

BACKGROUND: Adenosine levels rise during inflammation and modulate inflammatory responses by engaging with four different G protein-coupled receptors. It is suggested that adenosine exhibits pro-inflammatory effects through its A(1) receptor (A(1)R), and anti-inflammatory effects through A(2A) receptor (A(2A)R). Therefore, understanding of the mechanisms that govern adenosine receptor regulation may advance treatment of various inflammatory disorders. We previously reported that peak A(1)R expression during leukocyte recruitment, is followed by a peak in A(2A)R during inflammation resolution. PRINCIPAL FINDINGS: Here, we examined whether A(1)R activation sequentially induces A(2A)R expression and by this reverses inflammation. The effect of adenosine on A(1)R mediated A(2A)R expression was examined in peritoneal macrophages (PMPhi) and primary peritoneal mesothelial cells (PMC) in vitro. Induction of A(2A)R was inhibited by pertussis toxin (PTX) and partly dependent on A(2A)R stimulation. Administration of A(1)R agonists to healthy mice reduced A(1)R expression and induced A(2A)R production in PMC. Mice that were preconditioned with A(1)R agonists 24 hours before E. coli inoculation exhibited decreased TNFalpha and IL-6 sera levels and reduced leukocytes recruitment. Preconditioning was blocked by pretreatment with A(1)R antagonist, as well as, or by late treatment with A(2A)R antagonist, and was absent in A(2A)R(-/-) mice. CONCLUSIONS: Our data suggest that preconditioning by an A(1)R-agonist promotes the resolution of inflammation by inducing the production of A(2A)R. Future implications may include early treatment during inflammatory disorders or pretreatment before anticipated high risk inflammatory events, such as invasive surgery and organ transplantation.

Ketamine improves survival in burn injury followed by sepsis in rats.

Ketamine was reported to decrease cytokine production and improve survival after Escherichia coli-induced sepsis. We examined whether ketamine decreased interleukin (IL)-6 production and improved survival after 1) burn injury or 2) burn injury combined with sepsis (E. coli) at 24 h. Ketamine (10 mg/kg) or saline was given at 1 h after burn injury (G 1, 2, 5, 6), 24 h after burn injury (G 3, 4), or at E. coli inoculation (G 7, 8). Mortality was recorded for 7 days and IL-6 was measured in serum at 6 h after burn (G 1-2), 30 h after burn (G 3-4), or 6 h after sepsis (30 h after burn) (G 5-8). Burn injury only: Ketamine given immediately (1 h) after burn injury but not 24 h after, decreased the burn-induced increase of IL-6 but did not improve survival. Burn injury + sepsis: Ketamine given immediately after burn injury did not significantly decrease the sepsis-induced increase of IL-6 or improve survival. In contrast, ketamine given immediately after sepsis significantly improved survival (46.1% versus 13.3%, P = 0.008) and decreased IL-6 production (72,640 +/- 40,990 vs 332,300 +/- 32,300 pg/mL, P = 0.008). We conclude that ketamine therapy improves survival in burn injury followed by sepsis. This beneficial effect is probably achieved through interference with the inflammatory cascade, as evidenced by attenuation of the proinflammatory marker IL-6.

Correction of anemia in uremic mice by genetically modified peritoneal mesothelial cells.

BACKGROUND: During peritoneal dialysis, mesothelial cells become detached from the peritoneum and accumulate in the dialysate. Our aim was to evaluate the potential of peritoneal effluent (PF)-derived human peritoneal mesothelial cells (HPMC) as target for gene therapy. We used erythropoietin (EPO) as our target gene. METHODS: Various extracellular matrixes (ECM) were tested for optimal adhesion and growth of HPMC. The EPO gene was introduced to mouse peritoneal mesothelial cells (MPMC) and HPMC by transfection or retroviral transduction. EPO secretion from PMC was measured by enzyme-linked immunosorbent assay (ELISA) and by the TF-1 cell proliferation assay. We performed intraperitoneal or intramuscular transplantations of the genetically modified cells into regular or 5/6 nephrectomized Balb/c mice and nude mice. Finally, we measured serum EPO and hematocrit levels. RESULTS: ECM-coated plates provided up to sixfold increase in the efficiency of PMC isolation from PF. Gelatin coated dishes (20 microg/cm2) were found optimal for isolation of PF-HPMC. RPR-120535 liposome was found to be best for PMC transduction. In vitro studies showed EPO secretion from modified HPMC over 6 months. Intraperitoneal transplantation aided with collagen matrix was the most effective. EPO, in MPMC transplanted mice, was detected up to 3 weeks (peak at 13 +/- 1 mIU/mL), and anemia of uremic mice was corrected (35.3 +/- 0.9 mIU/mL to 41.9 +/- 1.1 mIU/mL). CONCLUSION: PF-HPMC can be considered as an appropriate target for gene therapy since these cells can be efficiently isolated, modified, and transplanted. Nevertheless, implantation techniques in the peritoneum should be directed at obtaining longer duration of transgene expression in vivo, and means should be developed for enabling regulated expression of the gene.