Jeremiah Johnson

Clinical Outcomes of Transplanted Modified Bone Marrow–Derived Mesenchymal Stem Cells in Stroke: A Phase 1/2a Study

Background and Purpose— Preclinical data suggest that cell-based therapies have the potential to improve stroke outcomes. Methods— Eighteen patients with stable, chronic stroke were enrolled in a 2-year, open-label, single-arm study to evaluate the safety and clinical outcomes of surgical transplantation of modified bone marrow–derived mesenchymal stem cells (SB623). Results— All patients in the safety population (N=18) experienced at least 1 treatment-emergent adverse event. Six patients experienced 6 serious treatment-emergent adverse events; 2 were probably or definitely related to surgical procedure; none were related to cell treatment. All serious treatment-emergent adverse events resolved without sequelae. There were no dose-limiting toxicities or deaths. Sixteen patients completed 12 months of follow-up at the time of this analysis. Significant improvement from baseline (mean) was reported for: (1) European Stroke Scale: mean increase 6.88 (95% confidence interval, 3.5–10.3; P<0.001), (2) National Institutes of Health Stroke Scale: mean decrease 2.00 (95% confidence interval, −2.7 to −1.3; P<0.001), (3) Fugl-Meyer total score: mean increase 19.20 (95% confidence interval, 11.4–27.0; P<0.001), and (4) Fugl-Meyer motor function total score: mean increase 11.40 (95% confidence interval, 4.6–18.2; P<0.001). No changes were observed in modified Rankin Scale. The area of magnetic resonance T2 fluid-attenuated inversion recovery signal change in the ipsilateral cortex 1 week after implantation significantly correlated with clinical improvement at 12 months (P<0.001 for European Stroke Scale). Conclusions— In this interim report, SB623 cells were safe and associated with improvement in clinical outcome end points at 12 months. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01287936.

Preoperative Onyx Embolization of Vascular Head and Neck Tumors by Direct Puncture

OBJECTIVE Preoperative embolization of hypervascular head and neck tumors is frequently performed to reduce operative times and blood loss. While traditional transarterial embolization is commonly used, direct tumoral puncture has also been advocated as an alternative. We report our series of head and neck tumors embolized with onyx via direct tumoral puncture to ascertain the safety and efficacy of embolization using this technique. METHODS We prospectively collected data on all head and neck tumors embolized with onyx at our institution during a 24-month period. RESULTS A total of 18 patients underwent preoperative embolization via direct tumoral puncture. Tumors included nine carotid body tumors, three glomus vagale tumors, five juvenile nasopharyngeal angiofibromas (JNAs), and one intracranial frontal parasagittal meningioma. All embolizations were completed in a single session. Mean fluoroscopy time was 40 minutes. The overall mean percent tumor devascularization was 87%. Inadvertent transtumoral migration of onyx into the superior sagittal sinus occurred during intraoperative embolization of the meningioma using single-plane fluoroscopy and resulted in a large postoperative hemorrhagic venous infarct. There were no other endovascular-related complications in the remaining patients embolized using biplanar fluoroscopy. CONCLUSION Embolization of hypervascular head and neck tumors with onyx via direct tumoral puncture can be performed safely and efficiently. Tumor embolization by direct puncture may theoretically lower the risk of inadvertent migration of onyx through nontarget arterial vessels, but may increase the risk of inadvertent transtumoral embolization of venous structures. Caution should be exercised when using this technique for intracranial pathologies, and the importance of biplanar fluoroscopy to allow better visualization of the onyx migration cannot be overemphasized.

Neurogenic stunned myocardium after acute hydrocephalus

Neurogenic stunned myocardium (NSM) is a syndrome of cardiac stunning after a neurological insult. It is commonly observed after aneurysmal subarachnoid hemorrhage but is increasingly being reported after other neurological events. The underlying mechanism of NSM is believed to be a hypothalamic-mediated sympathetic surge causing weakened cardiac contractility and even direct cardiac myocyte damage. The authors report 2 cases of NSM in pediatric patients after acute hydrocephalus. Both patients experienced severe cardiac dysfunction in the acute phase but ultimately had a good neurological outcome and a full cardiac recovery. The identification, treatment, and outcome in 2 rare pediatric cases of NSM are discussed, and the history of the brain-cardiac connection is reviewed.

Preoperative Embolization of Juvenile Nasopharyngeal Angiofibromas: Transarterial Versus Direct Tumoral Puncture

OBJECTIVE Preoperative embolization of juvenile nasopharyngeal angiofibromas (JNA) has been shown to reduce operative times and blood loss. Although traditional transarterial (TA) embolization is commonly used, direct tumoral puncture (DTP) has also been advocated as an alternative. We report our series of JNAs embolized with Onyx and compare the two embolization techniques. METHODS We retrospectively reviewed all JNAs embolized with Onyx at our institution during a 20-month period. The fluoroscopy time, percent of tumor devascularization, periprocedural complications, and intraoperative blood loss were compared between the two groups. RESULTS A total of 10 patients with JNA underwent preoperative embolization by a TA route (n = 5) or DTP (n = 5). Mean fluoroscopy time was 50 and 39 minutes in the TA and DTP groups, respectively. The mean percent tumor devascularization in the TA group was 77% compared with 93% in the DTP group. Intraoperative estimated blood loss in tumors embolized transarterially was higher than those embolized by DTP (862 mL vs. 412 mL); however, this difference did not reach statistical significance. There were no neurological complications related to the embolization procedures in either group. CONCLUSIONS Embolization of JNAs with Onyx can be performed safely by either method. Direct puncture is associated with shorter embolization procedure times and results in a greater degree of tumor devascularization. Although there was a trend toward lesser blood loss in patients embolized by DTP, it did not reach statistical significance in this small series. Larger series are needed to determine whether the improved tumor penetration achieved with DTP translates into clinical benefit.

Giant cell bone tumor of the thoracic spine presenting in late pregnancy.

BACKGROUND: We report a case of a large giant cell tumor of the thoracic spine presenting with spinal cord compression during pregnancy. CASE: A 24-year-old woman presented at term with lower back pain, bilateral lower extremity weakness, numbness, and bowel and bladder incontinence. Magnetic resonance imaging revealed a spinal soft tissue mass compressing the spinal cord. The patient delivered a healthy girl by cesarean then underwent a T8-T9 laminectomy, posterior spinal decompression, and instrument fusion. Two days later, she had a thoracotomy, corpectomy of the vertebral body, and anterior tumor debulking. Ultimately, the patient was discharged to inpatient rehabilitation with improved lower extremity strength and returned bowel and bladder function. CONCLUSION: Obstetricians should be vigilant regarding progressive neurologic symptoms during pregnancy.

Infarct growth despite full reperfusion in endovascular therapy for acute ischemic stroke

Aim To explore the predictors of infarct core expansion despite full reperfusion after intra-arterial therapy (IAT). Methods We retrospectively reviewed 604 consecutive patients who underwent IAT for anterior circulation large vessel occlusion acute ischemic stroke in two tertiary centers (2008–2013/2010–2013). Sixty patients selected by MRI or CT perfusion presenting within <24 h of onset with modified Thrombolysis In Cerebral Infarction (mTICI) grade 3 or 2c reperfusion were included. Significant infarct growth (SIG) was defined as infarct expansion >11.6 mL. Results Mean age was 67.0±13.7 years, 56% were men. Mean National Institute of Health Stroke Scale (NIHSS) score was 16.2±6.1, time from onset to puncture was 6.8±3.1 h, and procedure length was 1.3±0.6 h. MRI was used for baseline core analysis in 43% of patients. Mean baseline infarct volume was 17.1±19.1 mL, absolute infarct growth was 30.6±74.5 mL, and final infarct volume was 47.7±77.7 mL. Overall, 35% of patients had SIG. Three of 21 patients (14%) treated with stent-retrievers had SIG compared with 14 of 39 (36%) with first-generation devices. Eight of 21 patients (38%) with intravenous tissue plasminogen activator (IV t-PA) had infarct growth compared with 25/39 (64%) without. 23% of patients with SIG had a modified Rankin Scale score ≤2 at 3 months compared with 48% of those without SIG. Multivariate logistic regression indicated that race affected infarct growth. Use of IV t-PA (p=0.03) and stent-retrievers (p=0.03) were independently and inversely correlated with SIG. Conclusions Despite full reperfusion, infarct growth is relatively frequent and may explain poor clinical outcomes in this setting. Ethnicity was found to influence SIG. Use of IV t-PA and stent-retrievers were associated with less infarct core expansion.

Optic pathway infarct after Onyx HD 500 aneurysm embolization: visual pathway ischemia from superior hypophyseal artery occlusion

We report a case of visual deterioration after Onyx HD 500 embolization of a left 7 mm superior hypophyseal artery (SHA) aneurysm. After the procedure, the patient experienced a right incongruous homonymous hemianopia, and MRI showed an infarct of the ipsilateral optic chiasm/tract but no evidence of aneurysm mass effect or embolic cortical infarcts. The optic pathway ischemia is believed to be secondary to Onyx penetration and occlusion of an SHA branch near the aneurysm neck. Caution is advised when using liquid embolic agents to treat SHA aneurysms as SHA occlusion may lead to visual deficits.

Direct continuous measurement of draining vein pressure during Onyx embolization in a swine arteriovenous malformation model

Objective Periprocedural intracranial hemorrhage secondary to intranidal flow redirection may develop after arteriovenous malformation (AVM) embolization. We hypothesized that continuous draining vein pressure monitoring may identify clinically relevant hemodynamic changes during devascularization. Our goal was to characterize the draining vein pressures in a swine rete mirabile AVM model during embolization with Onyx. Methods An acute swine AVM model was constructed in six animals. Baseline, transoperative and final AVM area measurements were used to determine the degree of AVM embolization. Continuous video recordings were captured at 10 s intervals of active embolization. Draining vein pressure, arterial feeder pressure and heart rate were continuously monitored. Results The baseline and post-embolization mean draining vein pressures were 49.8±17.2 and 33.0±11.7 mm Hg (p=0.01), mean arterial pressures were 79.8±19.4 and 79.6±25.2 mm Hg (p=0.94), mean transnidal pressures were 35.8±19.7 and 45.4±33.7 mm Hg (p=0.37) and mean heart rates were 81.1±11.9 and 83.1±12.8 bpm (p=0.38), respectively. The draining vein pressure was averaged according to the degree of AVM embolization and represented as a relative change compared with the baseline draining vein pressure, and the slopes were found to decrease in all cases (p=0.02). In half of the animals the draining vein pressure decreased progressively as the AVM was embolized. In the remaining animals the venous pressure only started to decline after the AVM had been devascularized by > 50%. Conclusions The draining vein pressure response during Onyx embolization in the swine AVM model is heterogeneous. Continuous draining vein pressure monitoring is feasible and may potentially identify clinically relevant hemodynamic changes during AVM embolization.

The role of intra-arterial chemotherapy as an adjuvant treatment for glioblastoma

Abstract Glioblastoma multiforme (GBM) is an aggressive tumor with poor survival outcomes and limited treatment options. We conducted a literature review to compare the survival outcomes of intra-arterial (IA) and intravenous (IV) chemotherapy delivery for GBM. Nine studies of IA chemotherapy infusion with 301 total patients met our criteria for inclusion and three studies contained IV treatment groups for comparison (n = 230 for IA, n = 71 for IV). The studies were grouped by either using newly diagnosed or recurrent GBM patients. In the newly diagnosed group, IV chemotherapy produced a statistically higher median overall survival (MOS; 16.3 months) compared with IA treatment (14.02 months). However, the total number of adverse events in IA chemotherapy was 1.08 per patient whereas for IV it was higher at 1.54 events per patient. Our recurrent GBM group includes only patients treated with IA chemotherapy which resulted in an average MOS of 10.84 months. This group had 2.7 adverse events per patient but no IV group is available for comparison. Historically, the survival of patients with recurrent GBM ranges from 3 to 9 months (Gil-Gil et al. Bevacizumab for the treatment of glioblastoma. Clin Med Insights Oncol 2013;7:123–35). For this reason, we believe IA chemotherapy to be a viable methodology in recurrent GBM patients to prolong survival at the risk of procedure-related complications and in newly diagnosed patients with the benefit of decreased complications.

Does the ranking of surgeons in a publicly available online platform correlate with objective outcomes

OBJECTIVE The accuracy of public reporting in health care, especially from private vendors, remains an issue of debate. The authors investigated the association of the publicly reported physician complication rates in an online platform with real-world adverse outcomes of the same physicians for patients undergoing posterior lumbar fusion. METHODS The authors performed a cohort study involving physicians performing posterior lumbar fusions between 2009 and 2013 who were registered in the Statewide Planning and Research Cooperative System database. This cohort was merged with publicly available data over the same time period from ProPublica, a private company. Mixed-effects multivariable regression models were used to investigate the association of publicly available complication rates with the rate of discharge to a rehabilitation facility, length of stay, mortality, and hospitalization charges for the same surgeons. RESULTS During the selected study period, there were 8,457 patients in New York State who underwent posterior lumbar fusion performed by the 56 surgeons represented in the ProPublica Surgeon Scorecard over the same time period. Using a mixed-effects multivariable regression model, the authors demonstrated that publicly reported physician-level complication rates were not associated with the rate of discharge to a rehabilitation facility (OR 0.97, 95% CI 0.72-1.31), length of stay (adjusted difference -0.1, 95% CI -0.5 to 0.2), mortality (OR 0.87, 95% CI 0.49-1.55), and hospitalization charges (adjusted difference