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Yucatan miniature pigs (YMPs) are similar to humans in spinal cord size as well as physiological and neuroanatomical features, making them a useful model for human spinal cord injury. However, little is known regarding pig gait kinematics, especially on a treadmill. In this study, 12 healthy YMPs were assessed during bipedal and/or quadrupedal stepping on a treadmill at six speeds (1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 km/h). Kinematic parameters, including limb coordination and proximal and distal limb angles, were measured. Findings indicate that YMPs use a lateral sequence footfall pattern across all speeds. Stride and stance durations decreased with increasing speed whereas swing duration showed no significant change. Across all speeds assessed, no significant differences were noted between hindlimb stepping parameters for bipedal or quadrupedal gait with the exception of distal limb angular kinematics. Specifically, significant differences were observed between locomotor tasks during maximum flexion (quadrupedal > bipedal), total excursion (bipedal > quadrupedal), and the phase relationship between the timing of maximum extension between the right and left hindlimbs (bipedal > quadrupedal). Speed also impacted maximum flexion and right-left phase relationships given that significant differences were found between the fastest speed (3.5 km/h) relative to each of the other speeds. This study establishes a methodology for bipedal and quadrupedal treadmill-based kinematic testing in healthy YMPs. The treadmill approach used was effective in recruiting primarily the spinal circuitry responsible for the basic stepping patterns as has been shown in cats. We recommend 2.5 km/h (0.7 m/sec) as a target walking gait for pre-clinical studies using YMPs, which is similar to that used in cats.

Endovascular thrombectomy (ET) for acute large vessel occlusion reduces infarct size, and it should hypothetically decrease the incidence of major ischemic strokes requiring decompressive craniectomy (DC). The aim of this retrospective cohort study is to determine trends in the utilization of ET versus DC for stroke in the United States over a 10-year span.We extracted data from the Nationwide Inpatient Sample using International Classification of Diseases-9/10 codes from 2006-2016. Patients with a primary diagnosis of stroke were included. Baseline demographics, outcomes, and hospital charges were analyzed.The study cohort comprised 14,578,654 patients diagnosed with stroke. During the study period, DC and ET were performed in 124,718 and 62,637 patients, respectively. The number of stroke patients who underwent either ET or DC increased by 266% from 2006 to 2016. During that time period, the ET utilization rate increased (0.19% in 2006 to 14.07% in 2016, P0.0004), whereas the DC utilization rate decreased (7.07% in 2006 to 6.43% in 2016, P0.0001). In 2015, the utilization rate of ET (9.73%) exceeded that of DC (9.67%). ET-treated patients had shorter hospitalization durations (mean 8.8 vs. 16.8 days, P0.0001), lower mortality (16.2% vs. 19.3%), higher likelihood of discharge home (27.1% vs. 24.1%, P0.0001), and reduced hospital charges (mean $189,724 vs. $261,314, P0.0001).We identified an inverse relationship between national trends in rising ET and diminishing DC utilization for stroke treatment over a recent decade. Although direct causation cannot be inferred, our findings suggest that ET curtails the necessity for DC.

Ruptured vertebrobasilar dissecting aneurysms require urgent, often challenging treatment as they have with a high re-hemorrhage rate within the first 24 hours. The patient is a 57-year-old woman who presented with severe-sudden onset headache. Further work up showed a ruptured dissecting aneurysm of the caudal loop of the posterior inferior cerebellar artery (PICA) with associated narrowing distally, in the ascending limb. The aneurysm was immediately occluded with a Woven Endobridge (WEB) device (MicroVention, Tustin, CA, USA) while flow diversion treatment of the diseased ascending limb was postponed. Follow-up angiography three months later showed complete occlusion of the aneurysm, as well as healing of the diseased distal vessel, obviating the need for further intervention. WEB embolization of a ruptured dissecting posterior circulation aneurysm provided an excellent outcome for this patient.

Background Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder usually associated with specific medical conditions that cause a disturbance of the CNS homeostasis. It has seldom been reported to be a consequence of an iatrogenic intervention causing intracranial hypotension. Case presentation We report the case of an individual 69-year-old male presenting with headache and blurred vision following cerebrospinal fluid (CSF) leak from resection of a sellar mass. The patient developed the condition following removal of the lumbar drain post-operatively. Magnetic Resonance Imaging showed bilateral occipital, parieto-occipital, and cerebellar T2 FLAIR hyper-intensities, suggesting a radiological diagnosis of posterior reversible encephalopathy syndrome (PRES). The patient’s symptoms started to improve shortly afterwards and had completely resolved at 3 months follow-up. Conclusions The absence of severe hypertension and presence of an intraoperative CSF leak requiring placement of the lumbar drain suggests that decreased CSF volume and associated reactive hyperemia could have a role in the pathophysiology of the disease.

Mutant huntingtin (mHTT), the causative protein in Huntington’s disease (HD), associates with the translocase of mitochondrial inner membrane 23 (TIM23) complex, resulting in inhibition of synaptic mitochondrial protein import first detected in presymptomatic HD mice. The early timing of this event suggests that it is a relevant and direct pathophysiologic consequence of mHTT expression. We show that, of the 4 TIM23 complex proteins, mHTT specifically binds to the TIM23 subunit and that full-length wild-type huntingtin (wtHTT) and mHTT reside in the mitochondrial intermembrane space. We investigated differences in mitochondrial proteome between wtHTT and mHTT cells and found numerous proteomic disparities between mHTT and wtHTT mitochondria. We validated these data by quantitative immunoblotting in striatal cell lines and human HD brain tissue. The level of soluble matrix mitochondrial proteins imported through the TIM23 complex is lower in mHTT-expressing cell lines and brain tissues of HD patients compared with controls. In mHTT-expressing cell lines, membrane-bound TIM23-imported proteins have lower intramitochondrial levels, whereas inner membrane multispan proteins that are imported via the TIM22 pathway and proteins integrated into the outer membrane generally remain unchanged. In summary, we show that, in mitochondria, huntingtin is located in the intermembrane space, that mHTT binds with high-affinity to TIM23, and that mitochondria from mHTT-expressing cells and brain tissues of HD patients have reduced levels of nuclearly encoded proteins imported through TIM23. These data demonstrate the mechanism and biological significance of mHTT-mediated inhibition of mitochondrial protein import, a mechanism likely broadly relevant to other neurodegenerative diseases.

Traumatic spinal cord injury (SCI) is a devastating neurological condition that involves both primary and secondary tissue loss. Various cytotoxic events including hypoxia, hemorrhage and blood lysis, bioenergetic failure, oxidative stress, endoplasmic reticulum (ER) stress, and neuroinflammation contribute to secondary injury. The HIF prolyl hydroxylase domain (PHD/EGLN) family of proteins are iron-dependent, oxygen-sensing enzymes that regulate the stability of hypoxia inducible factor-1α (HIF-1α) and also mediate oxidative stress caused by free iron liberated from the lysis of blood. PHD inhibition improves outcome after experimental intracerebral hemorrhage (ICH) by reducing activating transcription factor 4 (ATF4)-driven neuronal death. As the ATF4-CHOP (CCAAT-enhancer-binding protein homologous protein) pathway plays a role in the pathogenesis of contusive SCI, we examined the effects of PHD inhibition in a mouse model of moderate T9 contusive SCI in which white matter damage is the primary driver of locomotor dysfunction. Pharmacological inhibition of PHDs using adaptaquin (AQ) moderately lowers acute induction of Atf4 and Chop mRNAs and prevents the acute decline of oligodendrocyte (OL) lineage mRNAs, but does not improve long-term recovery of hindlimb locomotion or increase chronic white matter sparing. Conditional genetic ablation of all three PHD isoenzymes in OLs did not affect Atf4, Chop or OL mRNAs expression levels, locomotor recovery, and white matter sparing after SCI. Hence, PHDs may not be suitable targets to improve outcomes in traumatic CNS pathologies that involve acute white matter injury.

COVID-19 patients are increasingly understood to develop multisystem manifestations, including neurologic involvement. We report the case of a 42-year old COVID-19 positive patient with a fatal intracerebral hemorrhage (ICH). The patient presented with fever and dyspnea, requiring intubation due to medical complications. After prolonged sedation and anticoagulation, the patient suddenly developed bilaterally fixed and dilated pupils, caused by a right-sided intracranial hemorrhage with uncal herniation. The course of this case illustrates the delicate balance between hypercoagulability and coagulation factor depletion; especially in the intubated and sedated patient, in whom regular neurological assessments are impeded. As we expand our understanding of the neurological ramifications of COVID-19, clinicians need to be increasingly aware of the precarious coagulation balance.

Introduction Pre-hospital identification of patients with large vessel occlusion (LVO) is critical in the timely triage of thrombectomy-eligible LVO patients to comprehensive stroke centers. The Rapid Arterial oCclusion Evaluation (RACE) scale was prospectively validated to identify LVO patients by EMS in Spain and has been widely adopted in the United States, though these healthcare infrastructure and EMS systems may differ significantly and these results may not be completely applicable in the US. This study prospectively validates the RACE scale as administered by US-based EMS personnel in the pre-hospital setting and we compare our results to the originally published results. Methods 232 adult patients suspected of having a stroke by EMS and transported to a participating comprehensive stroke center had the RACE scale administered prospectively and recorded in a secure web-based database. Admission NIHSS score and final diagnosis were recorded. Cerebrovascular imaging studies (CTA, MRA or DSA) were reviewed by a blinded, independent Neuroradiologist to determine LVO diagnosis. We used SAS and c-statistics to create receiver operating characteristic (ROC) curves to determine the area under the curve (AUC) and optimal cut point (CP) scores for the RACE scale. We also calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), overall accuracy for the optimal CP score. Results Our analysis of the predictive capability of the RACE scale showed similar predictive capacities for radiographically-confirmed LVO in patients prospectively tested in the US as compared to the original Spanish RACE scale population. The best CP score value predictive of LVO in our US-RACE study was determined to be ≥6, compared to the original Spanish study which was ≥5 (table 1). The overall prevalence of LVO as defined in our study was 13.4%, compared to a prevalence of 21.3% for the original paper’s definition of LVO. Conclusion This is the first prospective validation of the RACE scale performed in the US. These results demonstrate that the RACE scale retains the previously published predictive value in both the US and Spain in accurately identifying LVO stroke in a prehospital setting by EMS. Disclosures A. Cruz: None. E. Fortuny: None. B. Ugiliweneza: None. D. Wang: None. A. White: None. N. Khattar: None. S. Adams: None. B. Gallinore: None. D. Ding: None. S. Wolfe: None. D. Heck: None. R. James: None.

Introduction Accurate identification of large vessel occlusion (LVO) strokes in the pre-hospital setting is imperative to reduce time to thrombectomy and improve outcomes. Prior to this study, RACE was the only stroke severity scale designed to detect LVO that had been prospectively validated with Emergency Medical Services (EMS). The goal of our non-inferiority study is to prospectively validate and compare the novel PREDICT-3 item scale, PASS scale, and a composite of these two scales: the PREDICT Composite 4-item (PREDICT-4) scale to the RACE scale in detecting LVO in the prehospital setting. Methods Adult patients suspected of having a stroke by EMS and transported to a participating comprehensive stroke center had both PREDICT-4 and RACE scales administered prospectively and recorded in a secure web-based database. Admission NIHSS score and final diagnosis were also recorded. Cerebrovascular imaging studies (CTA, MRA or DSA) were reviewed by a blinded, independent neuroradiologist to determine LVO diagnosis. LVO was defined as occlusion of intracranial internal carotid artery (ICA), middle cerebral artery (MCA) M1 portion, or proximal aspect of single or multiple M2 branches of MCA, or basilar artery (BA). We used SAS and c-statistics to create receiver-operating characteristic (ROC) curves to determine the area under the curve (AUC) and optimal score cut point (CP) for each scale. We also calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy for each optimal CP score. Results 250 subjects were enrolled, 17 were excluded for lack of neurovascular imaging, 1 was excluded for incomplete stroke scale data, leaving 232 subjects who met inclusion criteria for analysis. 31 subjects had LVO and the prevalence of LVO was 13.4%. In table 1, we report the performance of each stroke severity scale at their respective optimal CP. In our study, the optimal CP for RACE was ≥6 while the original RACE study was ≥5. Conclusions This large, US-based, prospective, pre-hospital, EMS-administered study showed greater AUC for RACE. However, all three scales were non-inferior in AUC with respect to RACE. These newer, simpler scales may have acceptable diagnostic ability for LVO and be more easily adopted by EMS. Disclosures R. James: 1; C; Medtronic, Medtronic. A. Cruz: None. E. Fortuny: None. B. Ugiliweneza: None. D. Wang: None. A. White: None. N. Khattar: None. S. Adams: None. B. Gallinore: None. D. Ding: None. S. Wolfe: None. D. Heck: None.

Intro Accurate identification of large vessel occlusion (LVO) strokes in the field may save lives through reduced transport times. Emergency Medical Services (EMS) training is critical to the successful implementation of prehospital screening scales. The prospectively validated 6-item Rapid Arterial oCclusion Evaluation (RACE) scale is a common EMS LVO stroke scale. As part of our prospective, pre-hospital EMS Validation comparison study of the PRe-hospital ELVO Detection during Initial Care Transport (PREDICT) scale, we hypothesized that EMS providers without prior exposure to RACE would prefer the shorter, simpler PREDICT-4 scale and due to the cognitive bias known as the ‘mere exposure effect,’ EMS providers with previous experience with RACE will prefer it over the new PREDICT scale. Methods A total of 86 EMS providers were asked their preferred scale after performing both scales on a subject suspected of having a stroke. EMS providers were trained on a secure, online application to perform the PREDICT-4 scale and record both scales and complete a one-question survey (figure 1). A chi-square test and one-sample test of proportion was conducted to determine the preferred scale. Results 86 EMS providers enrolled a total of 250 subjects. 38 providers enrolled only one subject and 48 enrolled 2 or more. When comparing scale preference of all studied EMS providers (both with and without previous exposure to the RACE scale prior to this study), 37.2% preferred the PREDICT 4-item scale and 62.8% preferred the RACE scale, p=0.018, 95% CI [27.7, 47.8 and 52.2, 72.2, respectively]. The planned subgroup analysis of EMS providers who did not have prior mere-exposure to the RACE scale (n=49), we found that 34.7% preferred the PREDICT 4-item scale [95% CI 22.9, 48.6%] and 65.3% preferred the RACE scale p=0.03, 95% CI [51.3, 77.0]. In the subgroup analysis of the 48 providers who enrolled ≥2, on their first screening 20 (41.6%, p=0.248, 95% CI [28.8, 55.7]) preferred PREDICT-4 and 28 (58.3%) RACE. On their last screening, only 18 (37.5%, p=0.08, 95% CI [25.2, 51.6]) providers preferred PREDICT-4. Conclusion The shorter and simpler PREDICT scale was found to be less preferable with EMS provider all-comers, which may be partially due to the mere-exposure cognitive bias effect though this difference persisted in providers who had no prior exposure to either scale. In providers who enrolled multiple patients, there was a statistically insignificant trend towards preference for RACE between their first and last screening. Disclosures E. Fortuny: None. A. Cruz: None. B. Ugiliweneza: None. D. Wang: None. A. White: None. N. Khattar: None. B. Gallinore: None. D. Ding: None. S. Wolfe: None. D. Heck: None. R. James: 1; C; Medtronic.

Background Patients who survive aneurysmal subarachnoid hemorrhage (aSAH) are at risk for delayed neurological deficits (DND) and cerebral infarction. In this exploratory cohort comparison analysis, we compared in-hospital outcomes of aSAH patients administered a low-dose intravenous heparin (LDIVH) infusion (12 U/kg/h) vs those administered standard subcutaneous heparin (SQH) prophylaxis for deep vein thrombosis (DVT; 5000 U, 3 × daily). Objective To assess the safety and efficacy of LDIVH in aSAH patients. Methods We retrospectively analyzed 556 consecutive cases of aSAH patients whose aneurysm was secured by clipping or coiling at a single institution over a 10-yr period, including 233 administered the LDIVH protocol and 323 administered the SQH protocol. Radiological and outcome data were compared between the 2 cohorts using multivariable logistic regression and propensity score-based inverse probability of treatment weighting (IPTW). Results The unadjusted rate of cerebral infarction in the LDIVH cohort was half that in SQH cohort (9 vs 18%; P = .004). Multivariable logistic regression showed that patients in the LDIVH cohort were significantly less likely than those in the SQH cohort to have DND (odds ratio (OR) 0.53 [95% CI: 0.33, 0.85]) or cerebral infarction (OR 0.40 [95% CI: 0.23, 0.71]). Analysis following IPTW showed similar results. Rates of hemorrhagic complications, heparin-induced thrombocytopenia and DVT were not different between cohorts. Conclusion This cohort comparison analysis suggests that LDIVH infusion may favorably influence the outcome of patients after aSAH. Prospective studies are required to further assess the benefit of LDIVH infusion in patients with aSAH.

Background Annual incidence of symptomatic adjacent level disease (ALD) following lumbar fusion surgery ranges from 0.6% to 3.9% per year. Sagittal malalignment may contribute to the development of ALD. Objective To describe the relationship between pelvic incidence-lumbar lordosis (PI-LL) mismatch and the development of symptomatic ALD requiring revision surgery following single-level transforaminal lumbar interbody fusion for degenerative lumbar spondylosis and/or low-grade spondylolisthesis. Methods All patients who underwent a single-level transforaminal lumbar interbody fusion at either L4/5 or L5/S1 between July 2006 and December 2012 were analyzed for pre- and postoperative spinopelvic parameters. Using univariate and logistic regression analysis, we compared the spinopelvic parameters of those patients who required revision surgery against those patients who did not develop symptomatic ALD. We calculated the predictive value of PI-LL mismatch. Results One hundred fifty-nine patients met the inclusion criteria. The results noted that, for a 1° increase in PI-LL mismatch (preop and postop), the odds of developing ALD requiring surgery increased by 1.3 and 1.4 fold, respectively, which were statistically significant increases. Based on our analysis, a PI-LL mismatch of >11° had a positive predictive value of 75% for the development of symptomatic ALD requiring revision surgery. Conclusions A high PI-LL mismatch is strongly associated with the development of symptomatic ALD requiring revision lumbar spine surgery. The development of ALD may represent a global disease process as opposed to a focal condition. Spine surgeons may wish to consider assessment of spinopelvic parameters in the evaluation of degenerative lumbar spine pathology.

BACKGROUND Acute subdural hematomas (aSDHs) occur in approximately 10% to 20% of all closed head injury and represent a significant cause of morbidity and mortality in traumatic brain injury patients. Conventional craniotomy is an invasive intervention with the potential for excess blood loss and prolonged postoperative recovery time. OBJECTIVE To evaluate the outcomes of minimally invasive endoscopy for evacuation of aSDHs in a pilot feasibility study. METHODS We retrospectively reviewed the records of consecutive patients with aSDHs who underwent surgical treatment at our institution with minimally invasive endoscopy using the Apollo/Artemis Neuro Evacuation Device (Penumbra, Alameda, California) between April 2015 and July 2018. RESULTS The study cohort comprised three patients. The Glasgow Coma Scale on admission was 15 for all 3 patients, median preoperative hematoma volume was 49.5 cm3 (range 44-67.8 cm3), median postoperative degree of hematoma evacuation was 88% (range 84%-89%), and median modified Rankin Scale at discharge was 1 (range 0-3). CONCLUSION Endoscopic evacuation of aSDHs can be a safe and effective alternative to craniotomy in appropriately selected patients. Further studies are needed to refine the selection criteria for endoscopic aSDH evacuation and evaluate its long-term outcomes.

The anterior choroidal artery (AChA) supplies important cerebral structures such as the internal capsule, optic tract, and lateral geniculate body. It is normally a branch of the communicating segment of the internal carotid artery (ICA) with significant neurological symptomatology if injured. Typically, the AChA originates distal to the posterior communicating artery (PCoA), but rare variants have previously been described. Such anatomical differences are particularly important entities, especially in the context of neuroendovascular procedures, as inadvertent damage to these arteries can have devastating consequences. In this case report, we present an unusual anatomical pattern of the right AChA arising proximal to an ipsilateral fetal PCA.

Objective Acute traumatic cervical spinal cord injury (AcSCI) causes significant morbidity and has an impact on health care utilization. The aim of our study was to analyze health care utilization in patients undergoing surgical decompression and fusion for AcSCI based on timing and type of surgical approaches. Patient and methods Data were extracted using ICD9/10 and CPT codes from MarketScan (IBM Corp. Armonk, New York [v. 2000-2015]). We defined the comparative groups based on the timing of surgery (early 24 hours) and surgical approaches: anterior, posterior and circumferential. Outcomes of interest were: length of hospital stay, discharge disposition and health care utilization in the index hospitalization, within 30 days after discharge and 12 months following injury. Results Of 1604 patients, 80.9% had early procedures and 55.7% of these had anterior-only procedures. Overall, the median age was 46 years in the early surgery group and 47 years in the late surgery group. Patients in the early surgical group incurred higher outpatient services and there was no difference in cumulative median payments (index + 12 months) across the cohorts (early: $127,379, late: $121,049). The incidence of repeat surgery at the index level did not differ based on the timing of surgery (early 5% vs. late 7%). Complications were higher in the circumferential surgery cohort irrespective of the timing of surgery. Overall, combined median payment (index hospitalization + 12 months) was significantly higher for early circumferential cohorts compared to the anterior or posterior-only cohort ($195,990 and $109,977 vs. $121,236 respectively). Conclusion Late (>24 hours) surgeries were associated with a higher likelihood to be discharged home, lower utilization of outpatient services, higher hospital readmissions and no differences in payments (index and cumulative) compared to early surgeries. Circumferential approaches were associated with higher complication rates, lesser likelihood to be discharged home, higher utilization of outpatient services compared to anterior-only approaches.

Aneurysmal subarachnoid hemorrhage (aSAH) remains a significant cause of stroke disability despite gradual reductions in physical morbidity and mortality. Heparin is an effective anti-inflammatory agent and may potentially prevent delayed neurological injury in the days to weeks after the hemorrhage. Various human studies have shown the safety of a continuous infusion of low-dose unfractionated heparin in the setting of subarachnoid hemorrhage as well as its efficacy in minimizing delayed neurological deficits including symptomatic cerebral vasospasm, vasospasm-related infarction, and cognitive dysfunction. Studies have also shown mixed results with low-molecular-weight heparin usage in this patient population. Heparin treatment is not associated with significant hemorrhagic complications; however, vigilance is essential for early detection of heparin-induced thrombocytopenia in order to prevent devastating sequelae. Multicenter randomized controlled trials are necessary for objective characterization of the effects of heparin.

Aneurysmal subarachnoid hemorrhage (aSAH) remains a significant cause of stroke disability despite gradual reductions in physical morbidity and mortality. Heparin is an effective anti-inflammatory agent and may potentially prevent delayed neurological injury in the days to weeks after the hemorrhage. Various human studies have shown the safety of a continuous infusion of low-dose unfractionated heparin in the setting of subarachnoid hemorrhage as well as its efficacy in minimizing delayed neurological deficits including symptomatic cerebral vasospasm, vasospasm-related infarction, and cognitive dysfunction. Studies have also shown mixed results with low-molecular-weight heparin usage in this patient population. Heparin treatment is not associated with significant hemorrhagic complications; however, vigilance is essential for early detection of heparin-induced thrombocytopenia in order to prevent devastating sequelae. Multicenter randomized controlled trials are necessary for objective characterization of the effects of heparin.

Background Cerebral venous thrombosis (CVT) is a rare cerebrovascular disorder, comprising

Background Spontaneous intracranial hemorrhage (ICH) of the cerebellum can be life threatening because of mass effect on the brainstem and fourth ventricle. Suboccipital craniectomy is currently the treatment of choice for cerebellar ICH evacuation. Minimally invasive surgery (MIS) is currently being investigated for the treatment of supratentorial ICH. However, its utility for cerebellar ICH is unknown. The aim of this multicenter, retrospective cohort study is to evaluate the outcomes of MIS for cerebellar ICH. Methods We retrospectively reviewed the records of all patients with cerebellar ICH who underwent MIS using either the Apollo or Artemis Neuro Evacuation Device (Penumbra Inc., Alameda, California, USA) at 3 institutions from May 2015 to July 2018. Data from each contributing center were deidentified and pooled for analysis. Results The study cohort comprised 6 patients with a median age of 62.5 years. The median pre- and postoperative Glasgow Coma Scale scores were 10.5 and 15, respectively. The median degree of hematoma evacuation was 97.5% (range, 79%–100%). There were no procedural complications, but 1 patient required subsequent craniectomy (retreatment rate 17%). The median discharge modified Rankin scale score was 4, including 3 patients who improved to functional independence at follow-up durations of 3 months. Two patients died from medical complications (mortality rate 33%). Conclusions MIS could represent a reasonable alternative to conventional surgery for the treatment of appropriately selected patients with cerebellar ICH. However, further studies are needed to clarify the perioperative and long-term risk to benefit profiles of this technique.

Spinal cord herniation (SCH) is an uncommon traumatic event that should be considered in patients with vertebral fractures who develop an unusual constellation of autonomic and motor deficits. Herein, we describe a case of rapidly deteriorating neurological function following cervical spine fracture including sequelae such as bilateral lower-extremity weakness, loss of upper extremity motor function, and priapism. Decompression of the spinal cord allowed for the identification of the unusual herniation of the spinal cord and prevention of any further worsening of the neurological injury. Hyperflexion of the cervical spine upon traumatic impact provided the impetus for vertebral retropulsion and subsequent incarceration of the spinal cord. This phenomenon should be considered in the setting of acute traumatic injury to the cervical spinal cord. Surgical intervention is likely to allow the preservation of the remaining neurological function.

Cavernous hemangiomas with an intrasellar extension are very rare, generally benign lesions that manifest by the compression of nearby structures. The presenting symptoms usually range from visual disturbances to an endocrine imbalance. Occasional extension into the cavernous sinus has been reported, which can cause cranial nerve compression. We present the case of a 69-year-old man presenting with facial pain and decreased libido. On investigation, a lesion was identified and the parasellar region was homogeneously hyper-intense on gadolinium-enhanced magnetic resonance imaging (MRI). Endoscopic endonasal surgery remains one of the favored approaches for the resection of sellar lesions. Such pathology needs to remain on the neurosurgeon’s differential diagnosis, making an intraoperative frozen section of these lesions a useful tool in the surgeon's armamentarium, to guide further surgical resection.

OBJECTIVEThe development and recent widespread dissemination of flow diverters may have reduced the utilization of surgical bypass procedures to treat complex or giant unruptured intracranial aneurysms (UIAs). The aim of this retrospective cohort study was to observe trends in cerebral revascularization procedures for UIAs in the United States before and after the introduction of flow diverters by using the National (Nationwide) Inpatient Sample (NIS).METHODSThe authors extracted data from the NIS database for the years 1998–2015 using the ICD-9/10 diagnostic and procedure codes. Patients with a primary diagnosis of UIA with a concurrent bypass procedure were included in the study. Outcomes and hospital charges were analyzed.RESULTSA total of 216,212 patients had a primary diagnosis of UIA during the study period. The number of patients diagnosed with a UIA increased by 128% from 1998 (n = 7718) to 2015 (n = 17,600). Only 1328 of the UIA patients (0.6%) underwent cerebral bypass. The percentage of patients who underwent bypass in the flow diverter era (2010–2015) remained stable at 0.4%. Most patients who underwent bypass were white (51%), were female (62%), had a median household income in the 3rd or 4th quartiles (57%), and had private insurance (51%). The West (33%) and Midwest/North Central regions (30%) had the highest volume of bypasses, whereas the Northeast region had the lowest (15%). Compared to the period 1998–2011, bypass procedures for UIAs in 2012–2015 shifted entirely to urban teaching hospitals (100%) and to an elective basis (77%). The median hospital stay (9 vs 3 days, p < 0.0001), median hospital charges ($186,746 vs $66,361, p < 0.0001), and rate of any complication (51% vs 17%, p < 0.0001) were approximately threefold higher for the UIA patients with bypass than for those without bypass.CONCLUSIONSDespite a significant increase in the diagnosis of UIAs over the 17-year study period, the proportion of bypass procedures performed as part of their treatment has remained stable. Therefore, advances in endovascular aneurysm therapy do not appear to have affected the volume of bypass procedures performed in the UIA population. The authors’ findings suggest a potentially ongoing niche for bypass procedures in the contemporary treatment of UIAs.

Intracranial vascular pathologies often have overlapping clinical presentations. Dissected vessel occlusions and bifurcation aneurysms can appear similar on pretherapeutic imaging. The medical management of these two entities is drastically different. The patient is a 51-year-old man who presented with severe, sudden-onset headache. Initial presentation was consistent with a ruptured middle cerebral artery (MCA) aneurysm and surgical clipping was recommended. However, further review of radiographic findings could not definitively differentiate an aneurysmal origin of the symptoms as opposed to intracranial dissection followed by occlusion of the M2 branch of the MCA. MRI sampling perfection with application optimised contrasts using different flip angle evolution (SPACE) was performed and showed thin flow signalling distal to the dissected vessel stump confirming the diagnosis. Accurate diagnosis is a crucial step in directing treatment for intracranial vascular lesions. MRI SPACE is a simple tool in the diagnostic armamentarium to adequately direct treatment and avoid the potential for unnecessary interventions.

Various neurological diseases have recently been associated with neuroinflammation and worsening outcomes. Subarachnoid hemorrhage has been shown to generate a potent neuroinflammatory response. Heparin is a potential effective anti-inflammatory agent to prevent initial injury as well as delayed neurological decline. Different mechanisms of action for heparin have been proposed including, but not limited to the binding and neutralization of oxyhemoglobin, decreased transcription and signal transduction of endothelin-1, inhibition of binding to vessel wall selectins and vascular leakage into the subarachnoid space as well as direct binding and neutralization of inflammatory molecules. With a reasonably safe side-effect profile, heparin has shown significant promise in small series in human studies of aneurysmal subarachnoid hemorrhage in decreasing both initial and delayed neurological injury. Further studies are needed to validate various neuroprotective features of heparin in subarachnoid hemorrhage as well as other disease states.

Background and Purpose: Acute central retinal artery occlusion (CRAO) is a serious ophthalmologic emergency that may result in monocular blindness. To date, studies evaluating intra-arterial thrombolysis (IAT) have not shown a definitive clinical benefit. We have conducted a systematic review with a meta-analysis to effectively evaluate this treatment option. Methods: A systematic literature search was focused on studies containing five or more patients undergoing intra-arterial thrombolysis that included a control group treated with standard therapy. Pooled meta-analysis was performed. Results: Five retrospective controlled studies and one randomized clinical trial were identified satisfying all inclusion criteria resulting in the analysis of 236 patients treated with intra-arterial thrombolysis and 255 patients treated with standard therapy. A pooled fixed effects analysis resulted in an estimated odds ratio of 2.52, 95% CI [1.69, 3.77], (P

Devices and techniques for the endovascular treatment of intracranial aneurysms have rapidly progressed since their clinical debut nearly three decades ago. However, mastery of basic embolization techniques remains the cornerstone of successful endovascular therapy. Commonly employed techniques include direct, balloon-assisted, and stent-assisted coil embolization. The neuroendovascular field continues to innovate and coil embolization may not remain at the forefront of endovascular aneurysm treatment in the future. The introduction of innovative and promising new devices that do not utilize a coil platform may diminish the future importance of coil embolization techniques leading to a new age in aneurysm embolization where the coil is no longer the dominant device. In this chapter, we will discuss the basics of coil embolization focusing on standard direct, balloon-assisted, and stent-assisted techniques as they remain the workhorse options for aneurysm embolization.

Traumatic pseudoaneurysms of the middle meningeal artery (MMA) represent less than 1% of all intracranial aneurysms, and occur mostly in association with temporal bone fractures following head trauma. Given the unknown natural history, it is unclear whether they should be treated. We present two cases of MMA pseudoaneurysms discovered during trauma workups. The first patient is a 44-year-old male with severe traumatic brain injury (TBI) following a motor vehicle accident. The patient was found to have two right-sided middle meningeal artery pseudoaneurysms that were treated successfully with Onyx® (Medtronic, Minneapolis, MN) embolization. The second patient is a 56-year-old male that sustained a severe TBI and skull fracture following a motorcycle collision. Angiography demonstrated an unruptured right MMA aneurysm, which was also treated successfully with Onyx embolization. MMA pseudoaneurysms occur rarely in the setting of severe traumatic injuries. In select patients, treatment by an experienced neuro-interventionalist can prevent highly morbid future intracranial hemorrhages with minimal risk of complications.

International audience; G protein-coupled receptors ( GPCRs) are classically characterized as cell-surface receptors transmitting extracellular signals into cells. Here we show that central components of a GPCR signaling system comprised of the melatonin type 1 receptor (MT1), its associated G protein, and beta-arrestins are on and within neuronal mitochondria. We discovered that the ligand melatonin is exclusively synthesized in the mitochondrial matrix and released by the organelle activating the mitochondrial MT1 signal-transduction pathway inhibiting stress-mediated cytochrome c release and caspase activation. These findings coupled with our observation that mitochondrial MT1 overexpression reduces ischemic brain injury in mice delineate a mitochondrial GPCR mechanism contributing to the neuroprotective action of melatonin. We propose a new term, "automitocrine," analogous to "autocrine" when a similar phenomenon occurs at the cellular level, to describe this unexpected intracellular organelle ligand-receptor pathway that opens a new research avenue investigating mitochondrial GPCR biology.

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe type of stroke which carries a high case-fatality rate. Those who survive the ictus of aneurysm rupture harbor substantial risks of neurological morbidity, functional disability, and cognitive dysfunction. Although the pervasiveness of cognitive impairment is widely acknowledged as a long-term sequela of aSAH, the mechanisms underlying its development are poorly understood. The onset of aSAH elicits activation of the inflammatory cascade, and ongoing neuroinflammation is suspected to contribute to secondary complications, such as vasospasm and delayed cerebral ischemia. In this review, we analyze the extant literature regarding the relationship between neuroinflammation and cognitive dysfunction after aSAH. Pro-inflammatory cytokines appear to play a role in maintaining normal cognitive function in adults unaffected by aSAH. However, in the setting of aSAH, elevated cytokine levels may correlate with worse neuropsychological outcomes. This seemingly dichotomous relationship between neuroinflammation and cognition suggests that the action of cytokines varies, depending on their physiologic environment. Experimental therapies which suppress the immune response to aSAH appear to have a beneficial effect on cognitive outcomes. However, further studies are necessary to determine the utility of inflammatory mediators as biomarkers of neurocognitive outcomes, as well as their role in the management of aSAH.

Background Current guidelines suggest treating blood pressure above 180/105 mm Hg during the first 24 hours in patients with acute ischemic stroke undergoing any form of recanalization therapy. Currently, no studies exist to guide blood pressure management in patients with stroke treated specifically with mechanical thrombectomy. We aimed to determine the association between blood pressure parameters within the first 24 hours after mechanical thrombectomy and patient outcomes. Methods and Results We retrospectively studied a consecutive sample of adult patients who underwent mechanical thrombectomy for acute ischemic stroke of the anterior cerebral circulation at 3 institutions from March 2015 to October 2016. We collected the values of maximum, minimum, and average values of systolic blood pressure, diastolic blood pressure, and mean arterial pressures in the first 24 hours after mechanical thrombectomy. Primary and secondary outcomes were patients’ functional status at 90 days measured on the modified Rankin scale and the incidence and severity of intracranial hemorrhages within 48 hours. Associations were explored using an ordered multivariable logistic regression analyses. A total of 228 patients were included (mean age 65.8±14.3; 104 males, 45.6%). Maximum systolic blood pressure independently correlated with a worse 90‐day modified Rankin scale and hemorrhagic complications within 48 hours (adjusted odds ratio=1.02 [1.01–1.03], P =0.004; 1.02 [1.01–1.04], P =0.002; respectively) in multivariable analyses, after adjusting for several possible confounders. Conclusions Higher peak values of systolic blood pressure independently correlated with worse 90‐day modified Rankin scale and a higher rate of hemorrhagic complications. Further prospective studies are warranted to identify whether systolic blood pressure is a therapeutic target to improve outcomes.

OBJECTIVECognitive dysfunction occurs in up to 70% of aneurysmal subarachnoid hemorrhage (aSAH) survivors. Low-dose intravenous heparin (LDIVH) infusion using the Maryland protocol was recently shown to reduce clinical vasospasm and vasospasm-related infarction. In this study, the Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive changes in aSAH patients treated with the Maryland LDIVH protocol compared with controls.METHODSA retrospective analysis of all patients treated for aSAH between July 2009 and April 2014 was conducted. Beginning in 2012, aSAH patients were treated with LDIVH in the postprocedural period. The MoCA was administered to all aSAH survivors prospectively during routine follow-up visits, at least 3 months after aSAH, by trained staff blinded to treatment status. Mean MoCA scores were compared between groups, and regression analyses were performed for relevant factors.RESULTSNo significant differences in baseline characteristics were observed between groups. The mean MoCA score for the LDIVH group (n = 25) was 26.4 compared with 22.7 in controls (n = 22) (p = 0.013). Serious cognitive impairment (MoCA ≤ 20) was observed in 32% of controls compared with 0% in the LDIVH group (p = 0.008). Linear regression analysis demonstrated that only LDIVH was associated with a positive influence on MoCA scores (β = 3.68, p =0.019), whereas anterior communicating artery aneurysms and fevers were negatively associated with MoCA scores. Multivariable linear regression analysis resulted in all 3 factors maintaining significance. There were no treatment complications.CONCLUSIONSThis preliminary study suggests that the Maryland LDIVH protocol may improve cognitive outcomes in aSAH patients. A randomized controlled trial is needed to determine the safety and potential benefit of unfractionated heparin in aSAH patients.