Phase 1/2a Trial of ISPASM.

BACKGROUND AND PURPOSE: Microthrombosis could play a role in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Tirofiban has shown promising results in reducing delayed cerebral ischemia in retrospective studies. However, the safety of using tirofiban in aneurysmal subarachnoid hemorrhage is not rigorously established. METHODS: A phase 1/2a double-blinded randomized controlled trial (2:1 randomization) to assess the safety of a 7-day intravenous infusion of tirofiban compared with placebo, in patients with aneurysmal subarachnoid hemorrhage treated with ventriculostomy placed in the operative room and coiling was conducted. The primary end point was any intracranial hemorrhage during the hospital stay. The secondary end points were: incidence of radiographic and clinical vasospasm, incidence of delayed cerebral ischemia, and incidence of cerebral ischemic changes noted on magnetic resonance imaging or computed tomography. RESULTS: Eighteen patients received intravenous tirofiban and 12 received placebo. There was no difference in baseline characteristics except for higher male proportions in the tirofiban group. There was no difference in death, in development of new or change in existing intracranial hemorrhages, in thrombocytopenia, and need for shunts in the two arms. However, the tirofiban arm had a lower incidence of delayed cerebral ischemia compared with placebo (6% [1/18] versus 33% [4/12]; P=0.04), and less radiographic vasospasm as detected by catheter angiogram or computed tomography angiography (P=0.01) and computed tomography perfusion (P=0.01). CONCLUSIONS: The above preliminary results support proceeding with further testing of the safety and efficacy of 7-day intravenous infusion of tirofiban in a pragmatic (placing external ventricular drain by the bedside), multicenter setting, and using a larger population. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03691727.

Impact of Intracerebral Hematoma Evacuation During Decompressive Hemicraniectomy on Functional Outcomes.

BACKGROUND AND PURPOSE: Decompressive hemicraniectomy has been used to treat spontaneous intracerebral hemorrhage, but the benefit of evacuating the hematoma during the procedure is unclear. We aim to evaluate the utility of performing clot evacuation during hemicraniectomy for spontaneous intracerebral hemorrhage. METHODS: Retrospective cohort of consecutive patients (2010-2019) treated with decompressive hemicraniectomy for a spontaneous supratentorial intracerebral hemorrhage at the University of Iowa. We compared hemicraniectomy alone to hemicraniectomy plus hematoma evacuation. We analyzed clinical features and hematoma characteristics. The outcomes at 6 months were dichotomized into unfavorable (Glasgow Outcome Scale score 1-3) and favorable (Glasgow Outcome Scale score 4-5). RESULTS: Eighty-three patients underwent decompressive hemicraniectomy for spontaneous intracerebral hemorrhage, 52 with hematoma evacuation, and 31 without hematoma evacuation. There were no statistically significant differences in clinical and radiographic characteristics between the 2 groups. Evacuating the hematoma in addition to hemicraniectomy did not change the odds of favorable outcome at 6 months (P=0.806). CONCLUSIONS: In this retrospective study, the performance of hematoma evacuation during decompressive hemicraniectomy for spontaneous intracerebral hemorrhage may not change functional outcomes over performing the hemicraniectomy alone.

Concentration of Lp(a) (Lipoprotein[a]) in Aneurysm Sac Is Associated With Wall Enhancement of Unruptured Intracranial Aneurysm.

BACKGROUND AND PURPOSE: Atherosclerotic remodeling of the aneurysm wall, which could be detected as aneurysm wall enhancement (AWE) by magnetic resonance-vessel wall imaging, is a part of degenerative change of unruptured intracranial aneurysms (UIAs). The purpose of this study was to determine whether the luminal concentrations of atherosclerotic proteins in the aneurysm sac were associated with increased wall enhancement of UIAs in vessel wall imaging. METHODS: We performed a prospective study of subjects undergoing endovascular treatments for UIAs. All subjects underwent evaluation using 3T-magnetic resonance imaging, including pre/postcontrast vessel wall imaging of the UIAs. Blood samples were collected from the aneurysm sac and the parent artery during endovascular procedures. Presence/absence of AWE was correlated with the delta difference in concentration for each atherosclerotic protein between the lumen of UIA and in the parent artery. RESULTS: A total of consecutive 17 patients with 19 UIAs were enrolled. The delta difference of lipoprotein(a) was significantly higher in UIAs with AWE compared with those without AWE (-6.9±16.0 versus -45.4±44.9 µg/mL, P=0.03). CONCLUSIONS: Higher luminal concentrations of lipoprotein(a) in the aneurysm sac were significantly associated with increased wall enhancement of UIAs. A larger study is needed to confirm these findings.

Advances in the management of brain metastases from cancer of unknown primary.

Cancer of unknown primary accounts for 3-5% of all cancers for which an adequate investigation does not identify the primary tumor. The particular subset of brain metastasis in cancer of unknown primary (BMCUP) is a clinical challenge that lacks standardized diagnostic and therapeutic options. It is diagnosed predominantly in male patients in the sixth decade of age with complaints of headache, neurological dysfunction, cognitive and behavioral disturbances and seizures. The therapeutic approach to patients with BMCUP relies on local control and systemic treatment. Surgery or stereotactic radiosurgery and/or whole brain radiation therapy seems to be the cornerstone of the treatment approach to BMCUP. Systemic therapy remains essential as cancers of unknown primary are conceptually metastatic tumors. The benefits of chemotherapy were disappointing whereas those of targeted therapies and immune checkpoint inhibitors remain to be evaluated. In this Review, we address the advances in the diagnosis and treatment of BMCUP.

Novel technique for trialing peripheral nerve stimulation: ultrasonography-guided StimuCath trial.

OBJECTIVE Peripheral nerve stimulation (PNS) has been used for the treatment of neuropathic pain for many decades. Despite the specific indications for PNS, clinicians often have difficulty screening for candidates likely to have a good or fair outcome. Given the expense of a permanent implant, most insurance companies will not pay for the implant without a successful PNS trial. And since PNS has only recently been approved by the US Food and Drug Administration, many insurance companies will not pay for a conventional trial of PNS. The objective of this study is to describe a short low-cost method for trialing and screening patients for peripheral nerve stimulator implantation. Additionally, this study demonstrates the long-term efficacy of PNS in the treatment of chronic neuropathic pain and the relative effectiveness of this novel screening method. METHODS The records of all patients who had undergone trialing and implantation of a PNS system for chronic refractory pain at the authors' institution over a 1-year period (August 1, 2012-July 31, 2013) were examined in this retrospective case series. The search revealed 17 patients, 13 who had undergone a novel in-office ultrasonography-guided StimuCath screening technique and 4 who had undergone a traditional week-long screening procedure. All 17 patients experienced a successful PNS trial and proceeded to permanent PNS system implantation. Patients were followed up for a mean duration of 3.0 years. Visual analog scale (VAS) pain scores were used to assess pain relief in the short-term (< 6 weeks), at 1 year, and at the last follow-up. Final outcome was also characterized as good, fair, poor, or bad. RESULTS Of these 17 patients, 10 were still using their stimulator at the last follow-up, with 8 of them obtaining good relief (classified as ≥ 50% pain relief, with an average 81% reduction in the VAS score) and 2 patients attaining fair relief (< 50% relief but still using stimulation therapy). Among the remaining 7 patients, the stimulator had been explanted in 4 and there had been no relief in 3. Excluding explanted cases, follow-up ranged from 14 to 46 months, with an average of 36 months. Patients with good or fair relief had experienced pain prior to implantation for an average of 5.1 years (range 1.8-15.2 years). A longer duration of pain trended toward a poorer outcome (bad outcome 7.6 years vs good outcome 4.1 years, p = 0.03). Seven (54%) of the 13 patients with the shorter trial experienced a good or fair outcome with an average 79% reduction in the VAS score; however, all 4 of the bad outcome cases came from this group. Three (75%) of the 4 patients with the longer trial experienced a good or fair outcome at the last follow-up, with an average 54% reduction in the VAS score. There was no difference between the trialing methods and the proportion of favorable (good or fair) outcomes (p = 0.71). CONCLUSIONS Short, ultrasonography-guided StimuCath trials were feasible in screening patients for permanent implantation of PNS, with efficacy similar to the traditional week-long screening noted at the 3-year follow-up.

Long-Term Pain Reduction Does Not Imply Improved Functional Outcome in Patients Treated With Combined Supraorbital and Occipital Nerve Stimulation for Chronic Migraine.

BACKGROUND: Dual supraorbital and occipital nerve stimulation (SONS and ONS) have shown promising efficacy in treating primary headaches. However, its functional outcome is not well studied. OBJECTIVE: To present functional outcome studies of combined SONS and ONS for chronic migraine using verified metrics. METHOD: Consecutive patients with both SONS and ONS assessed with Migraine Disability Assessment (MIDAS) and Beck Depression Index (BDI) both preoperatively and postoperatively were studied. Selected predictor variables included patients with ≥50% improvement of pain, disability status, number of years from diagnosis to implantation, and narcotic use. Functional outcome variables included net improvement of ranked MIDAS and BDI scores. Multivariate analysis of variance was performed to assess the correlation between the outcome and predictor variables. RESULTS: Sixteen patients (12 female; average age 52 years old) were studied. Follow-up ranged from 5 to 80 months (average 44.5; σ = 21.4 months). At most recent follow-up, eight patients had a positive response (≥50% improvement in headache), which was the only predictor of functional outcome (total MIDAS, MIDAS-B, and BDI) (p = 0.021). Of note, improvement in functional outcome was only significant during the perioperative 3-6 months period and not throughout long-term follow-up. Among the predictor variables, a strong inverse correlation was found between disability status and positive response to stimulation (r = -0.582). CONCLUSION: There is a paucity of studies in quality of life, productivity, and psychosocial aspects with peripheral nerve stimulation therapy for headache. Patients with a positive response to SONS and ONS also reported overall improvement in their functional status as reflected by MIDAS and BDI in the perioperative period. Unfortunately, this effect waned over the long-term follow-up.

Hemorrhagic lumbar synovial cyst: case report and literature review.

Intraspinal synovial cysts are infrequent causes of back and radicular leg pain. Commonly associated with degenerative spinal disease, the majority of synovial cysts appear in the lumbar spine. Rarely, intracystic hemorrhage can occur through an unclear mechanism. Similarly rare, cysts may also become migratory. The pathogenesis of hemorrhagic synovial cysts remains uncertain and their potential for migration also remains unclear. A 36 year-old male presented to the clinic with 5 months of back pain and leg pain that began after a work-related injury. An initial MRI obtained by another surgeon 3 month prior demonstrated an epidural cystic mass with T1 hypointensity and T2 hyperintensity at L2-L3. With worsening pain, the patient came to our clinic for a second opinion. A second MRI demonstrated resolution of the L2-L3 epidural cystic mass and formation of a new epidural cystic mass at L3-L4 causing compression of the thecal sac. The patient subsequently underwent decompressive hemilaminectomy with cyst removal. We present a case of two lumbar synovial cysts, separated over time and a vertebral level and giving the appearance of a single, migratory cyst. This is the first case of an "occult migratory" synovial cyst with repeat MR imaging capturing spontaneous resolution of the initial cyst and formation of a hemorrhagic cyst one level below. We also present a summary of the 44 cases of hemorrhagic synovial cysts reported in the literature and propose a mechanism that may account for the hemorrhagic and migratory progression in some patients.

Unruptured Cerebral Aneurysms: Evaluation and Management.

The evolution of imaging techniques and their increased use in clinical practice have led to a higher detection rate of unruptured intracranial aneurysms. The diagnosis of an unruptured intracranial aneurysm is a source of significant stress to the patient because of the concerns for aneurysmal rupture, which is associated with substantial rates of morbidity and mortality. Therefore, it is important that decisions regarding optimum management are made based on the comparison of the risk of aneurysmal rupture with the risk associated with intervention. This review provides a comprehensive overview of the epidemiology, pathophysiology, natural history, clinical presentation, diagnosis, and management options for unruptured intracranial aneurysms based on the current evidence in the literature. Furthermore, the authors discuss the genetic abnormalities associated with intracranial aneurysm and current guidelines for screening in patients with a family history of intracranial aneurysms. Since there is significant controversy in the optimum management of small unruptured intracranial aneurysms, we provided a systematic approach to their management based on patient and aneurysm characteristics as well as the risks and benefits of intervention.

Flow diversion versus conventional treatment for carotid cavernous aneurysms.

BACKGROUND AND PURPOSE: Several endovascular treatment options are available for cavernous carotid aneurysms. We compared pipeline embolization device (PED) versus conventional endovascular treatment in terms of evolution of mass effect, complications, recurrence, and retreatment rate. METHODS: One hundred fifty-seven patients harboring 167 cavernous carotid aneurysms were treated using PED placement, coiling, stent-assisted coiling, and carotid vessel destruction. Procedural complications, angiographic results, and clinical outcomes were analyzed and compared. RESULTS: There were no difference in age, sex, and mean aneurysm size between those treated with PED and those treated with conventional endovascular procedures. The patients treated with PED had a significantly lower proportion of small-size aneurysms (<10 mm) and a shorter follow-up duration. Multivariate analysis revealed treatment other than PED (PED: odds ratio [OR], 0.03; P=0.002) and size >15 mm (OR, 4.27; P=0.003) to be predictors of no improvement in symptoms. The rate of complete occlusion was 81.36% (48 of 59) for PED, 42.25% (39 of 71) for stent-assisted coiling, 27.27% (6 of 22) for coiling, and 73.33% (11 of 15) for carotid vessel destruction. Retreatment was needed in patients with aneurysm size >15 mm (OR, 2.67; P=0.037) and those who were not treated with PED (PED: OR, 0.16; P=0.006). The rate of major complications was 6.6% (11 of 167). Patients who were treated with PED or stent-assisted coiling had 3.84 lower odds to develop complications (OR, 0.26; P<0.05). CONCLUSIONS: The use of PED should be encouraged, especially in symptomatic patients. We found PED to be associated with less need for future treatment, higher improvement in symptoms rate, and lower rate of complications.

Flow diversion for complex middle cerebral artery aneurysms.

INTRODUCTION: This study aims to evaluate the safety and efficacy of flow diversion for treatment of large and complex middle cerebral artery (MCA) aneurysms. METHODS: We conducted a retrospective review of the clinical charts of all patients who underwent Pipeline Embolization Device (PED) placement for aneurysm at our institution from October 2010 to October 2013. We included ten patients, of which five had large MCA aneurysms and three had giant ones. Fusiform unruptured aneurysms represented seven of all ten aneurysms. Angiographic and clinical follow-up were available for all patients mostly between 7 and 12 months. RESULTS: We had no technical complications, one periprocedural morbidity, and no mortality. On follow-up, we had no hemorrhagic complications, no aneurysms rupture, and only one clinically significant thromboembolic event in a patient who discontinued antiplatelet therapy against medical advice. One patient had completely occluded his diseased vessel but remained asymptomatic. The overall complication rate is 3/10. On follow-up, complete occlusion occurred in seven patients (7/9). CONCLUSION: PED treatment for large, giant, and bifurcation MCA aneurysms was feasible, with satisfying complete occlusion rate, no mortality, and reasonable morbidity rate.

Cerebral arteriovenous malformations: evaluation and management.

There has been increased detection of incidental AVMs as result of the frequent use of advanced imaging techniques. The natural history of AVM is poorly understood and its management is controversial. This review provides an overview of the epidemiology, pathophysiology, natural history, clinical presentation, diagnosis, and management of AVMs. The authors discussed the imaging techniques available for detecting AVMs with regard to the advantages and disadvantages of each imaging modality. Furthermore, this review paper discusses the factors that must be considered for the most appropriate management strategy (based on the current evidence in the literature) and the risks and benefits of each management option.

Management of head and neck pseudoaneurysms: a review of 33 consecutive cases.

BACKGROUND: Endosaccular coiling, vessel occlusion, stenting, stent-assisted coiling, and flow diversion are all endovascular treatment options for pseudoaneurysms (PAs) of the head and neck. We explore different clinical situations in which these were selected for PA management at a single institution. METHODS: Over a period of ten years, 33 patients presented to our hospital with PAs of the head and neck. Their outcomes and procedural complications are discussed. RESULTS: We observed a complication rate of 18.2% (6 of 33), consisting predominantly of infarcts following vessel occlusion. As measured by the modified Rankin Scale, 25 (75.8%) patients had achieved favorable outcomes on discharge. A single patient who was treated with stent-assisted coiling expired following procedural complications. CONCLUSIONS: In our series, most patients with traumatic/iatrogenic PAs were successfully treated with parent vessel sacrifice. When parent vessel occlusion is not an option, stenting with or without coiling, or flow diversion, may also be safe and effective alternatives.

Endovascular intervention for acute ischemic stroke in light of recent trials.

Three recently published trials, MR RESCUE, IMS III, and SYNTHESIS Expansion, evaluating the efficacy and safety of endovascular treatment of acute ischemic stroke have generated concerns about the future of endovascular approach. However, the tremendous evolution that imaging and endovascular treatment modalities have undergone over the past several years has raised doubts about the validity of these trials. In this paper, we review the role of endovascular treatment strategies in acute ischemic stroke and discuss the limitations and shortcomings that prevent generalization of the findings of recent trials. We also provide our experience in endovascular treatment of acute ischemic stroke.

Update on intra-arterial chemotherapy for retinoblastoma.

The tools for managing retinoblastoma have been increasing in the past decade. While globe-salvage still relies heavily on intravenous chemotherapy, tumors in advanced stage that failed chemotherapy are now referred for intra-arterial chemotherapy (IAC) to avoid enucleation. However, IAC still has many obstacles to overcome. We present an update on the indications, complications, limitations, success, and technical aspects of IAC. Given its safety and high efficacy, it is expected that IAC will replace conventional strategies and will become a first-line option even for tumors that are amenable for other strategies.

Predictors of infections following cranioplasty: a retrospective review of a large single center study.

INTRODUCTION: The variables that predispose to postcranioplasty infections are poorly described in the literature. We formulated a multivariate model that predicts the risk of infection in patients undergoing cranioplasty. METHOD: Retrospective review of all patients who underwent cranioplasty following craniectomy from January, 2000, to December, 2011. Tested predictors were age, sex, diabetic status, hypertensive status, reason for craniectomy, urgency status of craniectomy, location of cranioplasty, reoperation for hematoma, hydrocephalus postcranioplasty, and material type. A multivariate logistic regression analysis was performed. RESULTS: Three hundred forty-eight patients met the study criteria. Infection rate was 26.43% (92/348). Of these cases with infection, 56.52% (52/92) were superficial (supragaleal), 43.48% (40/92) were deep (subgaleal), and 31.52% (29/92) were present in both the supragaleal and subgaleal spaces. The predominant pathogen was coagulase-negative staphylococcus (30.43%) followed by methicillin-resistant Staphylococcus aureus (22.83%) and methicillin-sensitive Staphylococcus aureus (15.22%). Approximately 15.22% of all cultures were polymicrobial. Multivariate analysis revealed convex craniectomy, hemorrhagic stroke, and hydrocephalus to be associated with an increased risk of infection (OR = 14.41; P < 0.05, OR = 4.33; P < 0.05, OR = 1.90; P = 0.054, resp.). CONCLUSION: Many of the risk factors for infection after cranioplasty are modifiable. Recognition and prevention of the risk factors would help decrease the infection's rate.

Primary Embolization of Cerebral Arteriovenous Malformations With Intention to Cure: A Systematic Review of Literature and Meta-Analysis.

BACKGROUND AND OBJECTIVES: The treatment of brain arteriovenous malformations (AVMs) involves multiple approaches, including embolization, microsurgical resection, and radiosurgery. With the advent of new embolisates, dual-lumen balloon catheters, detachable tip microcatheters, and transvenous embolization, endovascular AVM obliteration has become more effective. Although adjuvant embolization and embolization are commonly used, the safety and effectiveness of curative embolization remain unclear. METHODS: We conducted a systematic literature review using PubMed, Ovid Medline, and Web of Science to identify studies reporting outcomes in patients with AVMs who underwent primary embolization with the intention to cure. We collected data on patient characteristics, AVM features, complications, and radiographic and clinical outcomes for meta-analysis. RESULTS: We identified 25 studies with a total of 1425 patients with 1427 AVMs who underwent curative embolization. Of these patients, 70% were low grade (pooled = 61% [39-82]), 67% were <3 cm (pooled = 78% [60-92]), and 75% were in superficial locations (pooled = 80% [72-86]). At last radiographic follow-up (mean, 16.7 ± 10.9 months), the full obliteration rate was 52% (pooled = 61% [43-77]) and retreatment rate was 25% (pooled = 17% [8.3-27]). At last clinical follow-up (mean, 24.2 ± 13.3 months), the poor clinical outcome rate was 7.9% (pooled = 4.4% [1.3-8.7]) and symptomatic complication rate was 13% (pooled = 13% [8-19]). There was no significant difference in the rate of radiographic cure, need for retreatment, and poor outcomes between ruptured and unruptured AVMs. Symptomatic complications were more common in the treatment of unruptured AVMs. The primary outcomes showed high heterogeneity (I2 = 72%-94%). CONCLUSION: Curative embolization of AVM is primarily reserved for small and low-grade AVMs, with highly variable outcomes. Our findings suggest poor radiographic outcomes and increased risk of complications. Outcomes are highly dependent on patient selection and technique used. Large multicenter prospective studies are required to further guide patient selection, categorize clinical and radiographic outcomes, and identify subgroup of patients that may benefit from curative embolization.

Neuromodulation with Ultrasound: Hypotheses on the Directionality of Effects and a Community Resource.

Low-intensity Transcranial Ultrasound Stimulation (TUS) is a promising non-invasive technique for deep-brain stimulation and focal neuromodulation. Research with animal models and computational modelling has raised the possibility that TUS can be biased towards enhancing or suppressing neural function. Here, we first conduct a systematic review of human TUS studies for perturbing neural function and alleviating brain disorders. We then collate a set of hypotheses on the directionality of TUS effects and conduct an initial meta-analysis on the human TUS study reported outcomes to date ( n = 32 studies, 37 experiments). We find that parameters such as the duty cycle show some predictability regarding whether the targeted area's function is likely to be enhanced or suppressed. Given that human TUS sample sizes are exponentially increasing, we recognize that results can stabilize or change as further studies are reported. Therefore, we conclude by establishing an Iowa-Newcastle (inTUS) resource for the systematic reporting of TUS parameters and outcomes to support further hypothesis testing for greater precision in brain stimulation and neuromodulation with TUS. Highlights: Systematic review of human TUS studies for enhancing or suppressing neural functionCollated set of hypotheses on using TUS to bias towards enhancement or suppressionMeta-analysis results identify parameters that may bias the directionality of effectsTUS resource established for systematic reporting of TUS parameters and outcomes.