Endovascular therapy versus microsurgical clipping of unruptured wide-neck aneurysms: a prospective multicenter study with propensity score analysis.

OBJECTIVE: Numerous techniques have been developed to treat wide-neck aneurysms (WNAs), each with different safety and efficacy profiles. Few studies have compared endovascular therapy (EVT) with microsurgery (MS). The authors' objective was to perform a prospective multicenter study of a WNA registry using rigorous outcome assessments and to compare EVT and MS using propensity score analysis (PSA). METHODS: Unruptured, saccular, not previously treated WNAs were included. WNA was defined as an aneurysm with a neck width ≥ 4 mm or a dome-to-neck ratio (DTNR) < 2. The primary outcome was modified Rankin Scale (mRS) score at 1 year after treatment (good outcome was defined as mRS score 0-2), as assessed by blinded research nurses and compared with PSA. Angiographic outcome was assessed using the Raymond scale with core laboratory review (adequate occlusion was defined as Raymond scale score 1-2). RESULTS: The analysis included 224 unruptured aneurysms in the EVT cohort (n = 140) and MS cohort (n = 84). There were no differences in baseline demographic characteristics, such as proportion of patients with good baseline mRS score (94.3% of the EVT cohort vs 94.0% of the MS cohort, p = 0.941). WNA inclusion criteria were similar between cohorts, with the most common being both neck width ≥ 4 mm and DTNR < 2 (50.7% of the EVT cohort vs 50.0% of the MS cohort, p = 0.228). More paraclinoid (32.1% vs 9.5%) and basilar tip (7.1% vs 3.6%) aneurysms were treated with EVT, whereas more middle cerebral artery (13.6% vs 42.9%) and pericallosal (1.4% vs 4.8%) aneurysms were treated with MS (p < 0.001). EVT aneurysms were slightly larger (p = 0.040), and MS aneurysms had a slightly lower mean DTNR (1.4 for the EVT cohort vs 1.3 for the MS cohort, p = 0.010). Within the EVT cohort, 9.3% of patients underwent stand-alone coiling, 17.1% balloon-assisted coiling, 34.3% stent-assisted coiling, 37.1% flow diversion, and 2.1% PulseRider-assisted coiling. Neurological morbidity secondary to a procedural complication was more common in the MS cohort (10.3% vs 1.4%, p = 0.003). One-year mRS scores were assessed for 218 patients (97.3%), and no significantly increased risk of poor clinical outcome was found for the MS cohort (OR 2.17, 95% CI 0.84-5.60, p = 0.110). In an unadjusted direct comparison, more patients in the EVT cohort achieved a good clinical outcome at 1 year (93.4% vs 84.1%, p = 0.048). Final adequate angiographic outcome was superior in the MS cohort (97.6% of the MS cohort vs 86.5% of the EVT cohort, p = 0.007). CONCLUSIONS: Although the treatments for unruptured WNA had similar clinical outcomes according to PSA, there were fewer complications and superior clinical outcome in the EVT cohort and superior angiographic outcomes in the MS cohort according to the unadjusted analysis. These results may be considered when selecting treatment modalities for patients with unruptured WNAs.

Endovascular Therapy Versus Microsurgical Clipping of Ruptured Wide Neck Aneurysms (EVERRUN Registry): a multicenter, prospective propensity score analysis.

OBJECTIVE: Randomized controlled trials have demonstrated the superiority of endovascular therapy (EVT) compared to microsurgery (MS) for ruptured aneurysms suitable for treatment or when therapy is broadly offered to all presenting aneurysms; however, wide neck aneurysms (WNAs) are a challenging subset that require more advanced techniques and warrant further investigation. Herein, the authors sought to investigate a prospective, multicenter WNA registry using rigorous outcome assessments and compare EVT and MS using propensity score analysis (PSA). METHODS: Untreated, ruptured, saccular WNAs were included in the analysis. A WNA was defined as having a neck ≥ 4 mm or a dome/neck ratio (DNR) < 2. The primary outcome was the modified Rankin Scale (mRS) score at 1 year posttreatment, as assessed by blinded research nurses (good outcome: mRS scores 0-2) and compared using PSA. RESULTS: The analysis included 87 ruptured aneurysms: 55 in the EVT cohort and 32 in the MS cohort. Demographics were similar in the two cohorts, including Hunt and Hess grade (p = 0.144) and modified Fisher grade (p = 0.475). WNA type inclusion criteria were similar in the two cohorts, with the most common type having a DNR < 2 (EVT 60.0% vs MS 62.5%). More anterior communicating artery aneurysms (27.3% vs 18.8%) and posterior circulation aneurysms (18.2% vs 0.0%) were treated with EVT, whereas more middle cerebral artery aneurysms were treated with MS (34.4% vs 18.2%, p = 0.025). Within the EVT cohort, 43.6% underwent stand-alone coiling, 50.9% balloon-assisted coiling, 3.6% stent-assisted coiling, and 1.8% flow diversion. The 1-year mRS score was assessed in 81 patients (93.1%), and the primary outcome demonstrated no increased risk for a poor outcome with MS compared to EVT (OR 0.43, 95% CI 0.13-1.45, p = 0.177). The durability of MS was higher, as evidenced by retreatment rates of 12.7% and 0% for EVT and MS, respectively (p = 0.04). CONCLUSIONS: EVT and MS had similar clinical outcomes at 1 year following ruptured WNA treatment. Because of their challenging anatomy, WNAs may represent a population in which EVT's previously demonstrated superiority for ruptured aneurysm treatment is less relevant. Further investigation into the treatment of ruptured WNAs is warranted.

Intracerebral Hemorrhage Volume Reduction and Timing of Intervention Versus Functional Benefit and Survival in the MISTIE III and STICH Trials.

BACKGROUND: The extent of intracerebral hemorrhage (ICH) removal conferred survival and functional benefits in the minimally invasive surgery with thrombolysis in intracerebral hemorrhage evacuation (MISTIE) III trial. It is unclear whether this similarly impacts outcome with craniotomy (open surgery) or whether timing from ictus to intervention influences outcome with either procedure. OBJECTIVE: To compare volume evacuation and timing of surgery in relation to outcomes in the MISTIE III and STICH (Surgical Trial in Intracerebral Hemorrhage) trials. METHODS: Postoperative scans were performed in STICH II, but not in STICH I; therefore, surgical MISTIE III cases with lobar hemorrhages (n = 84) were compared to STICH II all lobar cases (n = 259) for volumetric analyses. All MISTIE III surgical patients (n = 240) were compared to both STICH I and II (n = 722) surgical patients for timing analyses. These were investigated using cubic spline modeling and multivariate risk adjustment. RESULTS: End-of-treatment ICH volume ≤28.8 mL in MISTIE III and ≤30.0 mL in STICH II had increased probability of modified Rankin Scale (mRS) 0 to 3 at 180 d (P = .01 and P = .003, respectively). The effect in the MISTIE cohort remained significant after multivariate risk adjustments. Earlier surgery within 62 h of ictus had a lower probability of achieving an mRS 0 to 3 at 180 d with STICH I and II (P = .0004), but not with MISTIE III. This remained significant with multivariate risk adjustments. There was no impact of timing until intervention on mortality up to 47 h with either procedure. CONCLUSION: Thresholds of ICH removal influenced outcome with both procedures to a similar extent. There was a similar likelihood of achieving a good outcome with both procedures within a broad therapeutic time window.

Thrombolysis for Evacuation of Intracerebral and Intraventricular Hemorrhage: A Guide to Surgical Protocols With Practical Lessons Learned From the MISTIE and CLEAR Trials.

BACKGROUND: Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) procedure was recently tested in a large phase III randomized trial showing a significant probability of functional benefit in those cases that reached the goal hematoma evacuation of ≤15 mL residual (or ≥70% removal). Benefit of thrombolysis was also identified in cases with large intraventricular hemorrhage, and achieving at least 85% volume reduction in the Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) III trial. OBJECTIVE: To protocolize steps in the MISTIE and CLEAR procedures in order to maximize hematoma evacuation and minimize complications. METHODS: We articulate data-driven lessons and expert opinions surrounding the factors of patient selection, catheter placement, and dosing, which impacted safety and surgical performance in the MISTIE and CLEAR trials. RESULTS: Modifiable factors to maximize evacuation efficiency include optimizing catheter placement and pursuing aggressive dosing to achieve treatment goals, while strictly adhering to the safety steps as articulated in the respective trials. Prognostic factors that are viewed as nonmodifiable include greater initial intracerebral hemorrhage volume with irregular shape, smaller intraventricular bleeds, and the uncommon but consequential development of new bleeding during the dosing period despite strict protocol adherence. CONCLUSIONS: Surgeon education in this tutorial is aimed at maximizing the benefit of the MISTIE and CLEAR procedures by reviewing case selection, safety steps, treatment objectives, and technical nuances. Key lessons include stability imaging, etiology screening, and technical adherence to the protocol in order to achieve defined thresholds of evacuation.

Suboccipital, Supracerebellar, Infratentorial Approach for Microsurgical Clipping of a Ruptured Tentorial, Straight Sinus Type Dural Arteriovenous Fistula.

BACKGROUND: Dural arteriovenous fistulas (dAVFs) can often be successfully treated with endovascular embolization; however, surgery is occasionally still required. CASE DESCRIPTION: Herein, we discuss a 65-year-old male patient who presented with a Hunt-Hess IV subarachnoid hemorrhage, intraventricular hemorrhage, and cerebellar intracranial hemorrhage secondary to a ruptured Borden type III tentorial (straight sinus) dAVF. Angiography revealed supply from the left occipital and posterior meningeal arteries and direct drainage into the cerebellar cortical veins with venous aneurysms in both cerebellar hemispheres. Both transarterial and transvenous embolization were attempted, without success. Therefore, the patient was taken to the operating room for clip ligation of the dAVF. The operative video demonstrates a bilateral suboccipital craniotomy and supracerebellar infratentorial approach for surgical clipping of the dAVF. CONCLUSIONS: The case and operative video provide a valuable addition to surgical literature in an era where surgical management of dAVFs has become relatively rare.

Microsurgery for Unruptured Cerebral Arteriovenous Malformations in the National Inpatient Sample is More Common Post-ARUBA.

BACKGROUND: The ARUBA trial (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) was the first randomized control trial to investigate unruptured cerebral arteriovenous malformation (cAVM) treatments and concluded that medical management was superior to interventional therapy for the treatment of unruptured cAVMs. This conclusion generated considerable controversy and was followed by rebuttals and meta-analyses of the ARUBA methodology and results. We sought to determine whether the ARUBA results altered treatment trends of cAVMs within the United States. METHODS: Using the National Inpatient Sample, the largest all-payer inpatient care database within the United States, we isolated patients who were admitted on an elective basis for cAVM treatment and determined the treatment modality undergone by these patients. The cohort was dichotomized separately at 2 ARUBA time points: the European Stroke Conference presentation in May 2013, and The Lancet publication in February 2014. RESULTS: We found that the overall treatment rate of unruptured cAVMs decreased after both time points. However, the rate of surgical excision alone, relative to other modalities, was significantly increased, and endovascular intervention demonstrated a nonsignificant decrease. CONCLUSIONS: Our findings suggest that the ARUBA trial has influenced unruptured cAVM treatment patterns within the United States. Although the overall treatment rate has decreased, unruptured cAVMs, when treated post-ARUBA, are most commonly approached with surgical excision alone.

Survival After a Transcranial Bihemispheric Stabbing with a Knife: Case Report and Literature Review.

Low-velocity penetrating brain injuries (PBIs), also referred to as nonmissile brain injuries, typically result from stabbings, industrial or home accidents, or suicide attempts. A great deal of literature has focused on the injury patterns and management strategies of high-velocity PBIs. However, there are substantially fewer large, contemporary studies focused solely on low-velocity PBIs. Here, we present an interesting and uncommon case of a patient who suffered a bihemispheric stab wound involving the basal ganglia. A 22-year-old man presented to the hospital with a stab wound to the left calvarium. His initial Glasgow Coma Scale (GCS) score was 13, but he rapidly declined to a six and was intubated. He was emergently taken to the operating room for craniectomy, knife removal, and external ventricular drain placement. On the first postoperative day, the patient was following commands with all extremities. He was discharged to a rehabilitation facility 13 days postinjury. One year after the injury, the patient was free of major neurologic sequelae. This report illustrates a rare case of a good functional outcome after a transcranial stabbing with multiple imaging and exam findings usually associated with poor outcomes.

A randomized 500-subject open-label phase 3 clinical trial of minimally invasive surgery plus alteplase in intracerebral hemorrhage evacuation (MISTIE III).

RATIONALE AND HYPOTHESIS: Surgical removal of spontaneous intracerebral hemorrhage may reduce secondary destruction of brain tissue. However, large surgical trials of craniotomy have not demonstrated definitive improvement in clinical outcomes. Minimally invasive surgery may limit surgical tissue injury, and recent evidence supports testing these approaches in large clinical trials. METHODS AND DESIGN: MISTIE III is an investigator-initiated multicenter, randomized, open-label phase 3 study investigating whether minimally invasive clot evacuation with thrombolysis improves functional outcomes at 365 days compared to conservative management. Patients with supratentorial intracerebral hemorrhage clot volume ≥ 30 mL, confirmed by imaging within 24 h ofknown symptom onset,and intact brainstem reflexes were screened with a stability computed tomography scan at least 6 h after diagnostic scan. Patients who met clinical and imaging criteria (no ongoing coagulopathy; no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly; and stable hematoma size on consecutive scans) were randomized to either minimally invasive surgery plus thrombolysis or medical therapy. The sample size of 500 was based on findings of a phase 2 study. STUDY OUTCOMES: The primary outcome measure is dichotomized modified Rankin Scale 0-3 vs. 4-6 at 365 days adjusting for severity variables. Clinical secondary outcomes include dichotomized extended Glasgow Outcome Scale and all-cause mortality at 365 days; rate and extent of parenchymal blood clot removal; patient disposition at 365 days; efficacy at 180 days; type and intensity of ICU management; and quality of life measures. Safety was assessed at 30 days and throughout the study.

Surgical Performance Determines Functional Outcome Benefit in the Minimally Invasive Surgery Plus Recombinant Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation (MISTIE) Procedure.

BACKGROUND: Minimally invasive surgery procedures, including stereotactic catheter aspiration and clearance of intracerebral hemorrhage (ICH) with recombinant tissue plasminogen activator hold a promise to improve outcome of supratentorial brain hemorrhage, a morbid and disabling type of stroke. A recently completed Phase III randomized trial showed improved mortality but was neutral on the primary outcome (modified Rankin scale score 0 to 3 at 1 yr). OBJECTIVE: To assess surgical performance and its impact on the extent of ICH evacuation and functional outcomes. METHODS: Univariate and multivariate models were used to assess the extent of hematoma evacuation efficacy in relation to mRS 0 to 3 outcome and postulated factors related to patient, disease, and protocol adherence in the surgical arm (n = 242) of the MISTIE trial. RESULTS: Greater ICH reduction has a higher likelihood of achieving mRS of 0 to 3 with a minimum evacuation threshold of ≤15 mL end of treatment ICH volume or ≥70% volume reduction when controlling for disease severity factors. Mortality benefit was achieved at ≤30 mL end of treatment ICH volume, or >53% volume reduction. Initial hematoma volume, history of hypertension, irregular-shaped hematoma, number of alteplase doses given, surgical protocol deviations, and catheter manipulation problems were significant factors in failing to achieve ≤15 mL goal evacuation. Greater surgeon/site experiences were associated with avoiding poor hematoma evacuation. CONCLUSION: This is the first surgical trial reporting thresholds for reduction of ICH volume correlating with improved mortality and functional outcomes. To realize the benefit of surgery, protocol objectives, surgeon education, technical enhancements, and case selection should be focused on this goal.

Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial.

BACKGROUND: Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. METHODS: MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. FINDINGS: Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). INTERPRETATION: For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. FUNDING: National Institute of Neurological Disorders and Stroke and Genentech.

Opportunities and challenges in secondary stroke prevention: a mixed methods study.

Purpose: To describe control of risk factors after stroke from the perspectives of the stroke survivor, the family, and healthcare professionals.Materials and methods: A mixed methods design was used, undertaken in two phases: i) qualitative study using focus group methodology to explore secondary stroke prevention and ii) survey of stroke survivors about use of technology and self-management of blood pressure (BP).Results: From the eight focus groups (n = 33), three themes were identified: i) stroke is a wake-up call to do the right things; ii) challenges to doing the right things; and iii) role of technology in helping you to do the right things. Among survey respondents (n = 82), most participants reported mobile phone ownership (93%), mostly smartphones (66%), and >80% identified a greater role for technology in supporting management of risk factors. Participants who reported monitoring BP at home were significantly more likely to know their target BP than those not monitoring at home (83 vs. 42%; p < 0.001) and more adherent with medications (78 vs. 52%; p = 0.016).Conclusions: These findings highlight the ongoing challenges with achieving risk factor control after stroke and the potential to utilise health information technology to engage stroke survivors in self-management of their risk factors.Implications for rehabilitationClinicians should be knowledgeable of the challenges that stroke survivors face in managing their risk factors after stroke and the role that they can play in providing tailored education.BP continues to be poorly controlled after stroke and there is opportunity for improvement.Stroke survivors and their families are receptive to using health information technology to support their risk factor control.Rehabilitation clinicians have an opportunity to incorporate different aspects of health information technology into their practice to support self-management of risk factors.

Permanent CSF shunting after intraventricular hemorrhage in the CLEAR III trial.

OBJECTIVE: To study factors associated with permanent CSF diversion and the relationship between shunting and functional outcomes in spontaneous intraventricular hemorrhage (IVH). METHODS: Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III), a randomized, multicenter, double-blind, placebo-controlled trial, was conducted to determine if pragmatically employed external ventricular drainage (EVD) plus intraventricular alteplase improved outcome, in comparison to EVD plus saline. Outcome measures were predictors of shunting and blinded assessment of mortality and modified Rankin Scale at 180 days. RESULTS: Among the 500 patients with IVH, CSF shunting was performed in 90 (18%) patients at a median of 18 (interquartile range [IQR] 13-30) days. Patient demographics and IVH characteristics were similar among patients with and without shunts. In the multivariate analysis, black race (odds ratio [OR] 1.98; 95% confidence interval [CI] 1.18-3.34), duration of EVD (OR 1.10; CI 1.05-1.15), placement of more than one EVD (OR 1.93; CI 1.13-3.31), daily drainage CSF per 10 mL (OR 1.07; CI 1.04-1.10), and intracranial pressure >30 mm Hg (OR 1.70; CI 1.09-2.88) were associated with higher odds of permanent CSF shunting. Patients who had CSF shunts had similar odds of 180-day mortality, while survivors with shunts had increased odds of poor functional outcome, compared to survivors without shunts. CONCLUSIONS: Among patients with spontaneous IVH requiring emergency CSF diversion, those with early elevated intracranial pressure, high CSF output, and placement of more than one EVD are at increased odds of permanent ventricular shunting. Administration of intraventricular alteplase, early radiographic findings, and CSF measures were not useful predictors of permanent CSF diversion.

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial.

BACKGROUND: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. METHODS: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. FINDINGS: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88-1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90-1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41-0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22-3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31-0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64-0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37-3·91], p=0·771) was similar. INTERPRETATION: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status. FUNDING: National Institute of Neurological Disorders and Stroke.

Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial.

BACKGROUND: Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage. METHODS: MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany. We used a computer-generated allocation sequence with a block size of four to centrally randomise patients aged 18-80 years with a non-traumatic (spontaneous) intracerebral haemorrhage of 20 mL or higher to standard medical care or image-guided MIS plus alteplase (0·3 mg or 1·0 mg every 8 h for up to nine doses) to remove clots using surgical aspiration followed by alteplase clot irrigation. Primary outcomes were all safety outcomes: 30 day mortality, 7 day procedure-related mortality, 72 h symptomatic bleeding, and 30 day brain infections. This trial is registered with ClinicalTrials.gov, number NCT00224770. FINDINGS: Between Feb 2, 2006, and April 8, 2013, 96 patients were randomly allocated and completed follow-up: 54 (56%) in the MIS plus alteplase group and 42 (44%) in the standard medical care group. The primary outcomes did not differ between the standard medical care and MIS plus alteplase groups: 30 day mortality (four [9·5%, 95% CI 2·7-22.6] vs eight [14·8%, 6·6-27·1], p=0·542), 7 day mortality (zero [0%, 0-8·4] vs one [1·9%, 0·1-9·9], p=0·562), symptomatic bleeding (one [2·4%, 0·1-12·6] vs five [9·3%, 3·1-20·3], p=0·226), and brain bacterial infections (one [2·4%, 0·1-12·6] vs zero [0%, 0-6·6], p=0·438). Asymptomatic haemorrhages were more common in the MIS plus alteplase group than in the standard medical care group (12 [22·2%; 95% CI 12·0-35·6] vs three [7·1%; 1·5-19·5]; p=0·051). INTERPRETATION: MIS plus alteplase seems to be safe in patients with intracerebral haemorrhage, but increased asymptomatic bleeding is a major cautionary finding. These results, if replicable, could lead to the addition of surgical management as a therapeutic strategy for intracerebral haemorrhage. FUNDING: National Institute of Neurological Disorders and Stroke, Genentech, and Codman.

Older Stroke Patients with High Stroke Scores Have Delayed Door-To-Needle Times.

INTRODUCTION: The timely administration of intravenous (IV) tissue plasminogen activator (t-PA) to acute ischemic stroke patients from the period of symptom presentation to treatment, door-to-needle (DTN) time, is an important focus for quality improvement and best clinical practice. METHODS: A retrospective review of our Get With The Guidelines database was performed for a 5-hospital telestroke network for the period between January 2010 and January 2015. All acute ischemic stroke patients who were triaged in the emergency departments connected to the telestroke network and received IV t-PA were included. Optimal DTN time was defined as less than 60 minutes. Logistic regression was performed with clinical variables associated with DTN time. Age and National Institutes of Health Stroke Scale (NIHSS) score were categorized based on clinically significant cutoffs. RESULTS: Six-hundred and fifty-two patients (51% women, 46% White, 45% Hispanic, and 8% Black) were included in this study. The mean age was 70 years (range 29-98). Of the variables analyzed, only arrival mode, initial NIHSS score, and the interaction between age and initial NIHSS score were significant. DTN time more than or equal to 60 minutes was most common in patients aged more than 80 years with NIHSS score higher than 10. CONCLUSIONS: The cause of DTN time delay for older patients with higher NIHSS score is unclear but was not related to presenting blood pressure or arrival mode. Further study of this subgroup is important to reduce overall DTN times.

Functional Hemispherectomy for Refractory Status Epilepticus in 2 Adults.

BACKGROUND: Status epilepticus (SE) is a medical emergency, as deleterious long-term effects are well known. Medically induced burst suppression is often required if first-line and second-line treatments fail. Surgical intervention can be considered in some patients after prolonged treatment failure of medically induced coma. Multiple surgical options for terminating SE have been demonstrated in the literature, with only 2 reports including hemispherectomy in adults. CASE DESCRIPTION: We present 2 cases of adults with refractory SE who failed more conservative medical/surgical treatment but responded to functional hemispherectomy. Pertinent electroencephalography and imaging findings are discussed. In addition, all previously published pediatric and adult cases are briefly reviewed. CONCLUSIONS: Functional hemispherectomy can be considered in patients, including adults, with super-refractory SE and diffuse hemispheric onset. We report acceptable outcomes and quality of life in our 2 patients.

Cannabis Use and Outcomes in Patients With Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: The incidence of cannabis use in patients with aneurysmal subarachnoid hemorrhage (aSAH) and its impact on morbidity, mortality, and outcomes are unknown. Our objective was to evaluate the relationship between cannabis use and outcomes in patients with aSAH. METHODS: Records of consecutive patients admitted with aSAH between 2010 and 2015 were reviewed. Clinical features and outcomes of aSAH patients with negative urine drug screen and cannabinoids-positive (CB+) were compared. Regression analyses were used to assess for associations. RESULTS: The study group consisted of 108 patients; 25.9% with CB+. Delayed cerebral ischemia was diagnosed in 50% of CB+ and 23.8% of urine drug screen negative patients (P=0.01). CB+ was independently associated with development of delayed cerebral ischemia (odds ratio, 2.68; 95% confidence interval, 1.03-6.99; P=0.01). A significantly higher number of CB+ than urine drug screen negative patients had poor outcome (35.7% versus 13.8%; P=0.01). In univariate analysis, CB+ was associated with the composite end point of hospital mortality/severe disability (odds ratio, 2.93; 95% confidence interval, 1.07-8.01; P=0.04). However, after adjusting for other predictors, this effect was no longer significant. CONCLUSIONS: We offer preliminary data that CB+ is independently associated with delayed cerebral ischemia and possibly poor outcome in patients with aSAH. Our findings add to the growing evidence on the association of cannabis with cerebrovascular risk.

Early Hypoalbuminemia is an Independent Predictor of Mortality in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Hypoalbuminemia has been identified as a predictor of morbidity and mortality in critically ill patients. There is very little data on the significance and the prognostic value of hypoalbuminemia in patients with aneurysmal subarachnoid hemorrhage (aSAH). This study analyzed the impact of hypoalbuminemia on patient presentation, complications, and outcomes. METHODS: Records of patients admitted with aSAH were examined. Data on baseline characteristics, prevalence of delayed cerebral ischemia, and discharge outcomes were collected. Multivariable logistic regression analysis was performed to assess for associations. RESULTS: One-hundred and forty-two patients comprised the study cohort (mean age 54.6 ± 13.4), among which 45 (31.5 %) presented with hypoalbuminemia. No difference in baseline characteristics was noted between patients with hypoalbuminemia and those with normal serum albumin. The overall hospital mortality rate was significantly higher in patients with hypoalbuminemia, compared to those with normal albumin (28.9 % vs. 11.3 %; p = 0.04). Hypoalbuminemia was neither associated with delayed cerebral ischemia nor disability at discharge, but independently associated with in-hospital death (odds ratio: 4.26, 95 % confidence interval: 1.09-16.68; p = 0.04). CONCLUSION: In patients with aSAH, early hypoalbuminemia is an independent predictor of hospital mortality but not disability at discharge.

Proximal subcutaneous migration of the distal end of a ventriculoperitoneal shunt presenting with recurrent cerebrospinal fluid galactorrhea.

The authors report an unusual case of recurrent proximal migration of the distal end of a ventriculoperitoneal shunt catheter presenting as CSF galactorrhea. The authors review the pertinent literature and discuss the possible causes as well as techniques to prevent a similar occurrence.

Delayed post-traumatic spinal cord infarction in an adult after minor head and neck trauma: a case report.

INTRODUCTION: Delayed post-traumatic spinal cord infarction is a devastating complication described in children. In adults, spinal cord ischemia after cardiovascular interventions, scoliosis correction, or profound hypotension has been reported in the literature. However, delayed spinal cord infarction after minor head trauma has not been described yet. CASE PRESENTATION: We report the case of a 45-year-old Hispanic man who had a minor head trauma. He was admitted to our hospital because of paresthesias in his hands and neck pain. A radiological workup showed cervical spinal canal stenosis and chronic cervical spondylotic myelopathy. Twelve hours after admission, our patient became unresponsive and, despite full resuscitation efforts, died. The autopsy revealed spinal cord necrosis involving the entire cervical spinal cord and upper thoracic region. CONCLUSIONS: This case illustrates the extreme fragility of spinal cord hemodynamics in patients with chronic cervical spinal canal stenosis, in which any further perturbations, such as cervical hyperflexion related to a minor head injury, can have catastrophic consequences. Furthermore, the delayed onset of spinal cord infarction in this case shows that meticulous maintenance of blood pressure in the acute post-traumatic period is of paramount importance, even in patients with minimal post-traumatic symptoms.