Publications by authors named "Ben Waldau"

37 Publications

Mechanical Thrombectomy for Sequential Bilateral Middle Cerebral Artery Occlusions in a Patient With Recurrent Cryptogenic Strokes: A Case Report.

Neurohospitalist 2021 Jan 25;11(1):54-58. Epub 2020 Jun 25.

Department of Neurological Surgery, UC Davis Medical Center, Sacramento, CA, USA.

Recurrent sequential mechanical thrombectomy for cryptogenic large vessel occlusion (LVO) can lead to excellent clinical outcome. A 68-year-old right-handed male presented with an acute proximal right middle cerebral artery (MCA) ischemic syndrome and underwent successful revascularization by mechanical thrombectomy with normal functional recovery. He was treated with dual antiplatelet therapy for 2 months following discharge, however later discontinued clopidogrel due to side effects. He then developed a recurrent, contralateral MCA occlusion 16 months later and once again received emergent endovascular reperfusion therapy with excellent neurological outcome. He has remained on off-label empiric oral anticoagulation since and has not had recurrent stroke nor evidence of cerebral ischemia. Favorable clinical outcomes can be achieved in patients despite recurrent LVO who underwent emergent mechanical thrombectomy. Optimal antithrombotic secondary stroke prevention strategies following embolic stroke of unknown source remains uncertain as recent evidence does not support rivaroxaban or dabigatran over aspirin. The benefit of apixaban over aspirin for the prevention of recurrent cerebral ischemia is under current investigation.
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http://dx.doi.org/10.1177/1941874420934333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022181PMC
January 2021

Three-dimensional aneurysm volume measurements show no correlation between coil packing density and recurrence.

Heliyon 2020 Oct 8;6(10):e05170. Epub 2020 Oct 8.

Department of Neurological Surgery, University of California, Davis Medical Center, Sacramento, USA.

Objective: Endovascular treatment is the mainstay therapy for brain aneurysms. About 15% of patients need re-treatment within six months due to early recanalization. In this study, we investigate risk factors associated with treatment failure.

Methods: This retrospective cohort study includes endovascularly treated aneurysm cases between July 2012 and December 2015 at the University of California Davis Medical Center with pre-treatment and early post-treatment imaging. Thin cut 3D aneurysm volume rendering was used for morphologic analyses. Univariate and bivariate analyses were conducted to evaluate differences between patients and clinical factors by treatment failure.

Results: Of the 50 patients who met the inclusion criteria, 41 (82.0%) were female, with an average age of 61 years. Most aneurysms were on the anterior communicating artery (40%) or posterior communicating artery (22.0%), and 34 (68%) aneurysms were ruptured. Early treatment failure was observed in 14 (28.0%) of endovascularly treated patients. Raymond-Roy class (RRC) was significantly associated with treatment failure (p = 0.0052), with 10 out of the 14 cases (71.4%) with early recanalization having an RRC of 3. Coil packing density did not associate with aneurysm recanalization (p = 0.61).

Conclusion: In our single institution series, patient characteristics, aneurysm characteristics, or coil packing density did not affect early aneurysm recanalization. RRC was the best predictor of early recanalization; however, further confirmation with additional studies are required. Although this study focused on early treatment failure, late recanalization has been shown with longer follow up. Further investigation into factors associated with late treatment failure will need further investigation. New intrasaccular devices and flow diverters will also likely play a role in reducing recurrence in the future as these treatments gain usage.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551363PMC
October 2020

Ruptured Fisher grade 3 blister aneurysms have a higher incidence of delayed cerebral ischemia than ruptured Fisher grade 3 saccular aneurysms.

Brain Circ 2020 Apr-Jun;6(2):116-122. Epub 2020 Jun 26.

Department of Neurosurgery, UC Davis Medical Center, Sacramento, CA, USA.

Background: Blister aneurysms are a rare subclass of aneurysms, which remain challenging to treat both with open cerebrovascular and endovascular techniques, and clinicians continue to see poor outcomes in some cases despite improvements in technology. Based on our clinical observations, we hypothesized that patients with a Fisher grade 3 subarachnoid hemorrhage (SAH) from a ruptured anterior circulation blister aneurysm are significantly more likely to develop poor outcome due to delayed cerebral ischemia than patients with a Fisher grade 3 SAH from a ruptured anterior circulation saccular aneurysm.

Methods: In this consecutive case series, we reviewed management, outcomes, and rates of delayed cerebral ischemia for all ruptured anterior circulation blister aneurysms from 2012 to 2018 at our institution and compared them to a concurrent cohort of ruptured saccular anterior circulation aneurysms. A blister aneurysm was defined as an aneurysm that arises from a nonbranching point and demonstrates hemispherical anatomy on diagnostic angiography.

Results: We identified 14 consecutive ruptured anterior circulation blister aneurysms. Thirteen aneurysms were treated operatively- 5 with clip remodeling and 8 with flow diversion embolization. While clip remodeling had a high intraoperative rupture rate (80%), there was only one (12.5%) intraoperative rupture with flow diversion embolization. Outcomes were worsened by delayed cerebral ischemia from vasospasm in patients with Fisher 3 hemorrhages from blister aneurysms (86%). The rate of delayed cerebral ischemia from vasospasm was significantly higher for ruptured blister aneurysms than for a concurrent cohort of ruptured saccular aneurysms (8.6%, = 0.0001).

Conclusion: Ruptured Fisher grade 3 anterior circulation blister aneurysms have a significantly higher incidence of delayed cerebral ischemia from vasospasm compared to saccular aneurysms, regardless of the treatment modality.
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http://dx.doi.org/10.4103/bc.bc_63_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511919PMC
June 2020

Transradial access for thrombectomy in acute stroke: A systematic review and meta-analysis.

Clin Neurol Neurosurg 2020 11 18;198:106235. Epub 2020 Sep 18.

Department of Neurological Surgery, University of California, Davis, 4860 Y Street, Suite 3740, Sacramento, CA 95817, USA. Electronic address:

Objective: Transradial access has recently been gaining more popularity in various neurointerventional procedures. To this day, a systematic review and meta-analysis investigating the outcomes of transradial access for mechanical thrombectomy in acute stroke have not been performed.

Methods: PubMed, Embase, and Scopus databases were systematically searched. Studies published in the last ten years reporting on the use of transradial access for acute stroke intervention were eligible. The DerSimonian-Laird random effects model was used, and the primary endpoints included puncture to reperfusion time, end mRS, TICI reperfusion, mortality, and access site complications.

Results: A total of 515 records were identified. Fourteen observational studies reported on the use of radial access for thrombectomy, with 10 of these studies (n = 309) included in the meta-analysis. Mean puncture to reperfusion time associated with the transradial access was 46.864 ± 6.601 min. Favorable end mRS of ≤ 2 was reported in 37.1 % ± 7.3 % of patients. TICI ≥ 2B was achieved in 84.6 % ± 3.4 % of patients. All-cause mortality was observed in 9.3 % ± 4.8 % of patients. Transradial access had low complications with only 1.4 % ± 0.7 % of stroke cases. When the transradial studies were compared to the contemporary randomized clinical trials using the standard transfemoral access, no significant differences were found in all of these primary outcomes.

Conclusion: This meta-analysis study demonstrates that transradial access for mechanical thrombectomy in acute stroke may be a feasible and safe alternative. Future prospective studies are needed to validate these results.
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http://dx.doi.org/10.1016/j.clineuro.2020.106235DOI Listing
November 2020

Increased rupture risk in small intracranial aneurysms associated with methamphetamine use.

Interv Neuroradiol 2021 Feb 23;27(1):75-80. Epub 2020 Sep 23.

Department of Radiology, University of California Davis, Sacramento, CA, USA.

Background: Aneurysmal subarachnoid hemorrhage (SAH) is the most common cause of nontraumatic SAH. Current guidelines generally recommend observation for unruptured intracranial aneurysms smaller than 7 mm, for those are considered at low risk for spontaneous rupture according to available scoring systems.

Objective: We observed a tendency for SAH in small intracranial aneurysms in patients who are methamphetamine users. A retrospective, single center study to characterize the size and location of ruptured and unruptured intracranial aneurysms in methamphetamine users was performed.

Materials And Methods: Clinical characteristics and patient data were collected via retrospective chart review of patients with intracranial aneurysms and a history of methamphetamine use with a specific focus on aneurysm size and location.

Results: A total of 62 patients were identified with at least one intracranial aneurysm and a history of methamphetamine use, yielding 73 intracranial aneurysms (n = 73). The mean largest diameter of unruptured aneurysms (n = 44) was 5.1 mm (median 4.5, SD 2.5 mm), smaller than for ruptured aneurysms (n = 29) with a mean diameter of 6.3 mm (median 5.5, SD 2.5 mm). Aneurysms measuring less than 7 mm presented with SAH in 36.5%. With regard to location, 28% (n = 42) of anterior circulation aneurysms less than 7 mm presented with rupture, in contrast to 70% (n = 10) of posterior circulation aneurysms which were found to be ruptured.

Conclusions: Methamphetamine use may be considered a significant risk factor for aneurysmal SAH at a smaller aneurysm size than for other patients. These patients may benefit from a lower threshold for intervention and/or aggressive imaging and clinical follow-up.
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http://dx.doi.org/10.1177/1591019920959534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903554PMC
February 2021

Mechanical injury and blood are drivers of spatial memory deficits after rapid intraventricular hemorrhage.

Neurobiol Dis 2020 11 14;145:105084. Epub 2020 Sep 14.

Department of Neurological Surgery, UC Davis Medical Center, Sacramento, CA 95817, USA. Electronic address:

Aneurysmal intraventricular hemorrhage (IVH) survivors may recover with significant deficits in learning and memory. The goal of this study was to investigate the mechanism of memory decline after intraventricular aneurysm rupture. We developed an aneurysmal IVH rat model by injecting autologous, arterial blood over the period of two minutes into the right lateral ventricle. We also evaluated the effects of a volume-matched artificial cerebrospinal fluid (CSF) control, thrombin and the mode of delivery (pulsed hand injection versus continuous pump infusion). We performed magnetic resonance brain imaging after 1 and 5 weeks to evaluate for hydrocephalus and histological analysis of the dentate gyrus after 6 weeks. Only animals which underwent a whole blood pulsed hand injection had a spatial memory acquisition and retention deficit 5 weeks later. These animals had larger ventricles at 1 and 5 weeks than animals which underwent a continuous pump infusion of whole blood. We did not find a decline in dentate gyrus granule cell neurons or an impairment in dentate gyrus neurogenesis or differentiation 6 weeks after IVH. Rapid injections of blood or volume resulted in microglial activation in the dentate gyrus. In conclusion, our results point to mechanical injury as the predominant mechanism of memory decline after intraventricular aneurysmal rupture. However, volume-matched pulsed injections of artificial CSF did not create a spatial memory deficit at 5 weeks. Therefore, whole blood itself must play a role in the mechanism. Further research is required to evaluate whether the viscosity of blood causes additional mechanical disruption and hydrocephalus through a primary injury mechanism or whether the toxicity of blood causes a secondary injury mechanism that leads to the observed spatial memory deficit after 5 weeks.
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http://dx.doi.org/10.1016/j.nbd.2020.105084DOI Listing
November 2020

Impairment of glymphatic flow secondary to large terminal internal carotid artery aneurysm: Case report.

Clin Neurol Neurosurg 2020 10 26;197:106190. Epub 2020 Aug 26.

Department of Neurological Surgery, University of California Davis Health, 4860 Y Street Suite 3740, Sacramento, CA 95817, USA. Electronic address:

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http://dx.doi.org/10.1016/j.clineuro.2020.106190DOI Listing
October 2020

Cyclin D2-knock-out mice with attenuated dentate gyrus neurogenesis have robust deficits in long-term memory formation.

Sci Rep 2020 05 18;10(1):8204. Epub 2020 May 18.

Department of Neurological Surgery, UC Davis Medical Center, Sacramento, CA, 95817, US.

Neurobehavioral studies have produced contradictory findings concerning the function of neurogenesis in the adult dentate gyrus. Previous studies have proved inconsistent across several behavioral endpoints thought to be dependent on dentate neurogenesis, including memory acquisition, short-term and long-term retention of memory, pattern separation, and reversal learning. We hypothesized that the main function of dentate neurogenesis is long-term memory formation because we assumed that a newly formed and integrated neuron would have a long-term impact on the local neural network. We used a cyclin D2-knock-out (cyclin D2) mouse model of endogenously deficient dentate neurogenesis to test this hypothesis. We found that cyclin D2 mice had robust and sustained loss of long-term memory in two separate behavioral tasks, Morris water maze (MWM) and touchscreen intermediate pattern separation. Moreover, after adjusting for differences in brain volumes determined by magnetic resonance (MR) imaging, reduced dentate neurogenesis moderately correlated with deficits in memory retention after 24 hours. Importantly, cyclin D2 mice did not show deficits in learning acquisition in a touchscreen paradigm of intermediate pattern separation or MWM platform location, indicating intact short-term memory. Further evaluation of cyclin D2 mice is necessary to confirm that deficits are specifically linked to dentate gyrus neurogenesis since cyclin D2 mice also have a reduced size of the olfactory bulb, hippocampus, cerebellum and cortex besides reduced dentate gyrus neurogenesis.
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http://dx.doi.org/10.1038/s41598-020-65090-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235216PMC
May 2020

mRNA Expression Profiles from Whole Blood Associated with Vasospasm in Patients with Subarachnoid Hemorrhage.

Neurocrit Care 2020 08;33(1):82-89

Department of Neurology, University of California at San Francisco, San Francisco, USA.

Background: Though there are many biomarker studies of plasma and serum in patients with aneurysmal subarachnoid hemorrhage (SAH), few have examined blood cells that might contribute to vasospasm. In this study, we evaluated inflammatory and prothrombotic pathways by examining mRNA expression in whole blood of SAH patients with and without vasospasm.

Methods: Adult SAH patients with vasospasm (n = 29) and without vasospasm (n = 21) were matched for sex, race/ethnicity, and aneurysm treatment method. Diagnosis of vasospasm was made by angiography. mRNA expression was measured by Affymetrix Human Exon 1.0 ST Arrays. SAH patients with vasospasm were compared to those without vasospasm by ANCOVA to identify differential gene, exon, and alternatively spliced transcript expression. Analyses were adjusted for age, batch, and time of blood draw after SAH.

Results: At the gene level, there were 259 differentially expressed genes between SAH patients with vasospasm compared to patients without (false discovery rate < 0.05, |fold change| ≥ 1.2). At the exon level, 1210 exons representing 1093 genes were differentially regulated between the two groups (P < 0.005, ≥ 1.2 |fold change|). Principal components analysis segregated SAH patients with and without vasospasm. Signaling pathways for the 1093 vasospasm-related genes included adrenergic, P2Y, ET-1, NO, sildenafil, renin-angiotensin, thrombin, CCR3, CXCR4, MIF, fMLP, PKA, PKC, CRH, PPARα/RXRα, and calcium. Genes predicted to be alternatively spliced included IL23A, RSU1, PAQR6, and TRIP6.

Conclusions: This is the first study to demonstrate that mRNA expression in whole blood distinguishes SAH patients with vasospasm from those without vasospasm and supports a role of coagulation and immune systems in vasospasm.
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http://dx.doi.org/10.1007/s12028-019-00861-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392923PMC
August 2020

De Novo Blister Aneurysm Formation in 16 Days Associated with Mucorales Fungi.

Cureus 2019 Aug 1;11(8):e5301. Epub 2019 Aug 1.

Neurological Surgery, University of California, Davis Medical Center, Sacramento, USA.

Although blister aneurysms represent a small percentage of all intracranial aneurysms, they are generally considered to be a more morbid and challenging entity than the more common saccular intracranial aneurysms. Despite this, the etiology of blister aneurysms is still unknown, though there are several theories. We present the case of a 54-year-old man who initially presented with vision loss and normal intracranial computed tomography angiography imaging. Only 16 days thereafter, he underwent rapidly progressive clinical decline, which was found to be due to the development and rupture of a de novo supraclinoidal blister aneurysm. Autopsy results showed fungal infection of the arterial wall by Mucorales fungi at the site of the aneurysm. Our case report supports the theory that blister aneurysms can be caused by fungal infection of the wall of the internal carotid artery.
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http://dx.doi.org/10.7759/cureus.5301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768621PMC
August 2019

Bioengineering an Artificial Human Blood⁻Brain Barrier in Rodents.

Bioengineering (Basel) 2019 Apr 30;6(2). Epub 2019 Apr 30.

Department of Neurological Surgery, UC Davis Medical Center, Sacramento, CA 95811, USA.

Our group has recently created a novel in-vivo human brain organoid vascularized with human iPSC-derived endothelial cells. In this review article, we discuss the challenges of creating a perfused human brain organoid model in an immunosuppressed rodent host and discuss potential applications for neurosurgical disease modeling.
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http://dx.doi.org/10.3390/bioengineering6020038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630638PMC
April 2019

Using miniature brain implants in rodents for novel drug discovery.

Authors:
Ben Waldau

Expert Opin Drug Discov 2019 04 4;14(4):379-386. Epub 2019 Mar 4.

a Department of Neurological Surgery , University of California, Davis Medical Center , Sacramento , CA , USA.

Introduction: There continues to be a need to create an artificial human blood-brain barrier for pharmacological testing and modeling of diseases. Our group has recently vascularized human brain organoids with human iPSC-derived endothelial cells. Other groups have achieved brain organoid perfusion after vascularization with murine endothelial cells. Areas covered: This review article discusses the remaining hurdles, advantages, and limitations of creating a human organoid blood-brain barrier in rodents for novel drug discovery. Expert opinion: The creation of a human organoid blood-brain barrier in rodents will be feasible with appropriate molecular and cellular cues. An artificial human blood-brain barrier model may be used for pharmacological testing or for the study of the human blood-brain barrier in development or disease. Potential limitations of the model include an inferior competence of the blood-brain organoid barrier, the immunodeficient environment and low reproducibility due to variations in organoid morphology and vascularization. Despite its limitations, an artificial human blood-brain barrier model in rodents will further our understanding of blood-brain barrier pharmacology, and the field is expected to see significant advances in the next years.
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http://dx.doi.org/10.1080/17460441.2019.1577816DOI Listing
April 2019

Generation of human vascularized brain organoids.

Neuroreport 2018 05;29(7):588-593

Institute for Regenerative Cures (IRC).

The aim of this study was to vascularize brain organoids with a patient's own endothelial cells (ECs). Induced pluripotent stem cells (iPSCs) of one UC Davis patient were grown into whole-brain organoids. Simultaneously, iPSCs from the same patient were differentiated into ECs. On day 34, the organoid was re-embedded in Matrigel with 250 000 ECs. Vascularized organoids were grown in vitro for 3-5 weeks or transplanted into immunodeficient mice on day 54, and animals were perfused on day 68. Coating of brain organoids on day 34 with ECs led to robust vascularization of the organoid after 3-5 weeks in vitro and 2 weeks in vivo. Human CD31-positive blood vessels were found inside and in-between rosettes within the center of the organoid after transplantation. Vascularization of brain organoids with a patient's own iPSC-derived ECs is technically feasible.
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http://dx.doi.org/10.1097/WNR.0000000000001014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476536PMC
May 2018

Mycobacterium Genavense Granuloma Mimicking a Brain Tumor: A Case Report.

Cureus 2017 Aug 7;9(8):e1547. Epub 2017 Aug 7.

Neurological Surgery, University of California, Davis Medical Center.

Mycobacterium genavense (M. genavense) is a rare, non-tuberculous organism that commonly leads to gastrointestinal infections in immunocompromised patients. Only two cases of intracranial M. genavense infection have been reported to date. We describe a third case of M. genavense granuloma mimicking a right parietal intracranial mass, and review the literature on this exceedingly rare pathology.
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http://dx.doi.org/10.7759/cureus.1547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630459PMC
August 2017

Comparison of 3D TOF MR angiographic accuracy in predicting Raymond grade of flow-diverted versus coiled intracranial aneurysms.

J Clin Neurosci 2017 Aug 28;42:182-185. Epub 2017 Apr 28.

Department of Neurological Surgery, University of California, Davis, Sacramento, CA 95811, United States. Electronic address:

The accuracy of 3D time of Flight Magnetic Resonance Angiography (TOF MRA) has been studied extensively for following coiled intracranial aneurysms. It is used by many clinicians for non-invasive follow-up because of its adequate sensitivity in predicting aneurysmal recanalization compared to diagnostic cerebral angiography. The data on the accuracy of 3D TOF MRA for the Pipeline™ Embolization Device (PED) are sparse. In a retrospective chart review, we compared the accuracy of 3D TOF MRA of PED to coil embolization at our institution. 3D TOF MRA had a lower sensitivity and positive predictive value in detecting aneurysmal filling in PED-treated versus coiled aneurysms (57% versus 87% and 80% versus 100%, respectively). Analysis of discrepancies between conventional diagnostic angiography and 3D TOF MRA revealed that 3D TOF MRA was inaccurate in the setting of small residual necks and slow residual filling of the dome with fluid-fluid layers. Therefore, contrasted studies such as contrast-enhanced MRA may be preferred for non-invasively following PED-treated aneurysms to increase accuracy.
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http://dx.doi.org/10.1016/j.jocn.2017.03.009DOI Listing
August 2017

Surgical and Nonsurgical Treatment of Vascular Skull Base Trauma.

J Neurol Surg B Skull Base 2016 Oct 24;77(5):396-403. Epub 2016 May 24.

Department of Neurosurgery, UC Davis Medical Center, Sacramento, California, United States.

Vascular trauma is associated with blunt skull base fractures and penetrating injuries. We review the contemporary management of cranial vascular trauma, including blunt and penetrating cerebrovascular injury as well as refractory epistaxis from facial trauma.
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http://dx.doi.org/10.1055/s-0036-1583539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5023434PMC
October 2016

Inhibition of Src family kinases improves cognitive function after intraventricular hemorrhage or intraventricular thrombin.

J Cereb Blood Flow Metab 2017 Jul 1;37(7):2359-2367. Epub 2016 Jan 1.

1 Department of Neurology and the M.I.N.D. Institute, University of California at Davis, Sacramento, USA.

Intraventricular hemorrhage causes spatial memory loss, but the mechanism remains unknown. Our recent studies demonstrated that traumatic brain injury activates Src family kinases, which cause spatial memory loss. To test whether the spatial memory loss was due to blood in the ventricles, which activated Src family kinases, we infused autologous whole blood or thrombin into the lateral ventricles of adult rats to model non-traumatic intraventricular hemorrhage. Hippocampal neuron loss was examined 1 day to 5 weeks later. Spatial memory function was assessed 29 to 33 days later using the Morris water maze. Five weeks after the ventricular injections of blood or thrombin, there was death of most hippocampal neurons and significant memory deficits compared with sham operated controls. These data show that intraventricular thrombin is sufficient to kill hippocampal neurons and produce spatial memory loss. In addition, systemic administration of the non-specific Src family kinase inhibitor PP2 or intraventricular injection of siRNA-Fyn, a Src family kinase family member, prevented hippocampal neuronal loss and spatial memory deficits following intraventricular hemorrhage. The data support the conclusions that thrombin mediates the hippocampal neuronal cell death and spatial memory deficits produced by intraventricular blood and that these can be blocked by non-specific inhibition of Src family kinases or by inhibiting Fyn.
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http://dx.doi.org/10.1177/0271678X16666291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531336PMC
July 2017

Resolution of third nerve palsy despite persistent aneurysmal mass effect after flow diversion embolization of posterior communicating artery aneurysms.

J Clin Neurosci 2016 Sep 12;31:207-9. Epub 2016 May 12.

Department of Neurosurgery, UC Davis Medical Center, 2315 Stockton Blvd., Sacramento, CA 95817, USA. Electronic address:

Posterior communicating artery (PCOM) aneurysms may cause third nerve palsies. The optimal treatment with clipping versus coiling remains controversial. Here we report on two cases of resolution of third nerve palsy after flow diversion embolization of large and giant PCOM aneurysms without adjuvant coil placement. The resolution of third nerve palsy was not preceded by significant shrinkage of the aneurysmal sac on MRI. However, one patient showed resolution of T2-weighted signal abnormalities in the midbrain and mesial temporal lobe despite a similar size of the aneurysm. Therefore, flow diversion embolization of a PCOM aneurysm may resolve oculomotor nerve palsies through decreasing arterial pulsations against the nerve or midbrain.
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http://dx.doi.org/10.1016/j.jocn.2016.02.027DOI Listing
September 2016

Management and outcome of spontaneous cerebral venous sinus thrombosis in a 5-year consecutive single-institution cohort.

J Neurointerv Surg 2017 Jan 19;9(1):34-38. Epub 2016 Apr 19.

Department of Neurological Surgery, University of California-Davis Medical Center, Sacramento, California, USA.

Background: Cerebral venous sinus thrombosis (CVST) is an uncommon form of stroke with a variable presentation, ranging from headaches, to coma and death. Although the American Stroke Association has developed guidelines for the treatment of CVST, data are sparse on the outcome after treatment with anticoagulation, thrombolysis, and thrombectomy.

Methods: In this retrospective review, we describe the 5-year UC Davis experience with spontaneous CVST.

Results: Forty-one patients (mean age 37.5±23.1, range 0-96 years; 29 female) were identified with CVST. The majority of cases involved the transverse sinus (75.6%), sigmoid sinus (58.5%), and superior sagittal sinus (29.3%). The most common form of treatment was anticoagulation or antiplatelet therapy (n=35), while six patients were managed by observation alone. The overall 1-year modified Rankin score (mRS) was 1.4±1.5. Male patients and patients with a poor admission mRS had a worse outcome. Outcome was unaffected by hypercoagulable state, number of dural sinuses involved, the presence of intracranial hemorrhage, or seizures. Two patients who underwent anticoagulation therapy also required endovascular thrombectomy; both patients had a 1-year mRS of ≤2. Two patients underwent direct open surgical canalization of the superior sagittal sinus with varying outcomes (mRS 2 vs mRS 6).

Conclusions: In our series, the majority (92.9%) of patients with spontaneous dural sinus thrombosis had a favorable clinical outcome as defined by a mRS ≤2. Further prospective studies are needed to study the impact of anticoagulation on the clinical course of the disease.
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http://dx.doi.org/10.1136/neurintsurg-2015-012237DOI Listing
January 2017

Morphometric Analysis of Predictors of Cervical Syrinx Formation in the Setting of Chiari I Malformation.

Pediatr Neurosurg 2016 13;51(3):137-41. Epub 2016 Feb 13.

Duke University Medical Center, Durham, N.C., USA.

Background/aims: We performed a morphometric analysis of Chiari I malformations to look for predictors of cervical syrinx formation.

Methods: Eighteen patients with Chiari I malformation and associated cervical syrinx and 16 patients with Chiari I malformation without associated cervical syrinx were included in the study. Chiari I size was obtained from the radiology report; foramen magnum diameter, cerebellar volume, posterior fossa volume and intracranial volume were calculated using OsiriX software, and average measurements were compared between the two groups.

Results And Conclusion: Patients with Chiari I with syrinx had an average tonsillar descent of 13.03 ± 5.31 mm compared to 9.25 ± 3.31 mm in the Chiari I without syrinx group (p < 0.05). Patients with Chiari I and syrinx also showed increased cerebellar crowding with a higher cerebellar volume to posterior fossa volume ratio; however, this difference was not significant (0.83 vs. 0.81; p = 0.1872). No difference between groups was found in posterior fossa volume, intracranial volume and foramen magnum diameter. Therefore, only Chiari I size based on the extent of tonsillar herniation was found to be a determinant of cervical syrinx formation.
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http://dx.doi.org/10.1159/000442991DOI Listing
January 2017

The vascular stem cell niche: roadmap for transplanted neural progenitor cells during environmental enrichment?

Authors:
Ben Waldau

Neural Regen Res 2015 Aug;10(8):1204-5

Department of Neurosurgery, UC Davis Medical Center, 4860 Y Street, ACC 3740, Sacramento 95817, CA, USA.

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http://dx.doi.org/10.4103/1673-5374.162692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590221PMC
August 2015

Contrast encephalopathy after coiling in the setting of obstructive sleep apnoea.

BMJ Case Rep 2015 Sep 25;2015. Epub 2015 Sep 25.

Department of Neurosurgery, UC Davis, Sacramento, California, USA.

Obstructive sleep apnoea (OSA) is increasingly recognised as a source of perioperative morbidity and mortality. We describe a patient with severe OSA who developed transient contrast encephalopathy after elective coiling of an anterior communicating artery aneurysm. Contrast extravasation led to cerebral oedema, seizures and delirium, which eventually completely resolved. OSA is known to be associated with a proinflammatory state that leads to hypertension, impaired endothelial repair capacity and endothelial dysfunction. Further studies are needed to clarify whether OSA increases the risk of endovascular procedures.
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http://dx.doi.org/10.1136/bcr-2014-207503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4593243PMC
September 2015

Efficient Generation of Induced Pluripotent Stem and Neural Progenitor Cells From Acutely Harvested Dura Mater Obtained During Ventriculoperitoneal Shunt Surgery.

World Neurosurg 2015 Nov 11;84(5):1256-66.e1. Epub 2015 Jun 11.

Department of Neurosurgery, UC Davis Medical Center, Sacramento, California, USA; UC Davis Stem Cell Program, Sacramento, California, USA. Electronic address:

Background: The dura mater can be easily biopsied during most cranial neurosurgical operations. We describe a protocol that allows for robust generation of induced pluripotent stem cells (iPSCs) and neural progenitors from acutely harvested dura mater.

Objective: To generate iPSCs and neural progenitor cells from dura mater obtained during ventriculoperitoneal shunt surgery.

Methods: Dura was obtained during ventriculoperitoneal shunt surgery for normal pressure hydrocephalus from a 60-year-old patient with severe cognitive impairment. Fibroblasts were isolated from the dural matrix and transduced with nonintegrating Sendai virus for iPSC induction. A subset of successfully generated iPSC clones underwent immunocytochemical analysis, teratoma assay, karyotyping, and targeted neural differentiation.

Results: Eleven iPSC clones were obtained from the transduction of an estimated 600,000 dural fibroblasts after 3 passages. Three clones underwent immunocytochemical analysis and were shown to express the transcription factors OCT-4, SOX2, and the embryonic cell markers SSEA-4, TRA-1-60, and Nanog. Two clones were tested for pluripotency and formed teratomas at the injection site in immunodeficient mice. Three clones underwent chromosomal analysis and were found to have a normal metaphase spread and karyotype. One clone underwent targeted neural differentiation and formed neural rosettes as well as TuJ1/SOX1-positive neural progenitor cells.

Conclusions: IPSCs and neural progenitor cells can be efficiently derived from the dura of patients who need to undergo cranial neurosurgical operations. IPSCs were obtained with a nonintegrating virus and exhibited a normal karyotype, making them candidates for future autotransplantation after targeted differentiation to treat functional deficits.
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http://dx.doi.org/10.1016/j.wneu.2015.05.076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602677PMC
November 2015

CrossFit-related cervical internal carotid artery dissection.

Emerg Radiol 2015 Aug 28;22(4):449-52. Epub 2015 Apr 28.

Department of Radiology, University of California Davis Medical Center, 4860 Y Street, Suite 3100, Sacramento, CA, 95817, USA,

CrossFit is a high-intensity strength and conditioning program that has gained popularity over the past decade. Potential injuries associated with CrossFit training have been suggested in past reports. We report three cases of cervical carotid dissection that are associated with CrossFit workouts. Patient 1 suffered a distal cervical internal carotid artery (ICA) dissection near the skull base and a small infarct in Wernicke's area. He was placed on anticoagulation and on follow-up has near complete recovery. Patient 2 suffered a proximal cervical ICA dissection that led to arterial occlusion and recurrent middle cerebral artery territory infarcts and significant neurological sequelae. Patient 3 had a skull base ICA dissection that led to a partial Horner's syndrome but no cerebral infarct. While direct causality cannot be proven, intense CrossFit workouts may have led to the ICA dissections in these patients.
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http://dx.doi.org/10.1007/s10140-015-1318-5DOI Listing
August 2015

Transplanted Dentate Progenitor Cells Show Increased Survival in an Enriched Environment But Do Not Exert a Neurotrophic Effect on Spatial Memory Within 2 Weeks of Engraftment.

Cell Transplant 2015 23;24(12):2435-48. Epub 2015 Jan 23.

Department of Neurosurgery, University of California, Davis, Sacramento, CA, USA.

Cyclin D2 knockout mice show decreased levels of endogenous dentate neurogenesis. We investigated whether transplanted dentate progenitor cells from wild-type mice respond in vivo to an enriched environment and whether they improve deficient dentate neurogenesis through a neurotrophic effect. Adult cyclin D2 knockout mice were transplanted with passaged adult progenitor cells and kept in an enriched environment or under standard housing conditions in isolation. After 1 week, animals living in an enriched environment underwent water maze testing. Progenitor cells grown on a laminin/poly-d-lysine monolayer expressed Sox2 and nestin and could be differentiated in vitro into neurons and astrocytes. After transplantation into the dentate gyrus, cells preferentially survived along the laminin-rich ependymal lining of the basal cistern or basal membrane of capillaries. A subpopulation of transplanted cells migrated into the interstitial space of the hippocampus and was not associated with laminin. Environmental enrichment led to a significant increase in the survival of transplanted progenitor cells on laminin in the dentate gyrus after 2 weeks. However, animals did not show an enhanced performance in the Morris water maze, and transplantation failed to exert a neurotrophic effect on endogenous neurogenesis after 2 weeks. However, a major limitation of the study is the short-term period of investigation, which may have been insufficient to capture functional effects. In conclusion, initial survival of transplanted neural progenitor cells was dependent on the presence of laminin and was significantly enhanced by environmental enrichment. Further studies are needed to address whether an enriched environment continues to promote graft survival over longer periods of time.
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http://dx.doi.org/10.3727/096368915X687011DOI Listing
October 2016

Prominin-1 allows prospective isolation of neural stem cells from the adult murine hippocampus.

J Neurosci 2013 Feb;33(7):3010-24

CRTD-Center for Regenerative Therapies Dresden, Technische Universität Dresden, 01307 Dresden, Germany.

Prominin-1 (CD133) is commonly used to isolate stem and progenitor cells from the developing and adult nervous system and to identify cancer stem cells in brain tumors. However, despite extensive characterization of Prominin-1(+) precursor cells from the adult subventricular zone, no information about the expression of Prominin-1 by precursor cells in the subgranular zone (SGZ) of the adult hippocampus has been available. We show here that Prominin-1 is expressed by a significant number of cells in the SGZ of adult mice in vivo and ex vivo, including postmitotic astrocytes. A small subset of Prominin-1(+) cells coexpressed the nonspecific precursor cell marker Nestin as well as GFAP and Sox2. Upon fluorescence-activated cell sorting, only Prominin-1/Nestin double-positive cells fulfilled the defining stem cell criteria of proliferation, self-renewal, and multipotentiality as assessed by a neurosphere assay. In addition, isolated primary Prominin-1(+) cells preferentially migrated to the neurogenic niche in the SGZ upon transplantation in vivo. Finally, despite its expression by various stem and progenitor cells, Prominin-1 turned out to be dispensable for precursor cell proliferation in vitro and in vivo. Nevertheless, a net decrease in hippocampal neurogenesis, by ∼30% was found in Prominin-1 knock-out mice, suggesting other roles in controlling adult hippocampal neurogenesis. Remarkably, an upregulation of Prominin-2 was detected in Prominin-1-deficient mice highlighting a potential compensatory mechanism, which might explain the lack of severe symptoms in individuals carrying mutations in the Prom1 gene.
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http://dx.doi.org/10.1523/JNEUROSCI.3363-12.2013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619213PMC
February 2013

Transient complete lower facial nerve palsy after craniotomy for aneurysm clipping.

Br J Neurosurg 2013 Apr 30;27(2):241-2. Epub 2012 Aug 30.

Department of Surgery (Neurosurgery), Duke University Medical Center, Durham, NC 27710, USA.

We present the case of a 41-year old female who developed a complete facial nerve palsy after an interhemispheric approach for clipping of a distal anterior cerebral artery aneurysm. Work-up revealed that she had developed acute parotitis during surgery, possibly from obstruction of the parotid duct by the tracheal tube.
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http://dx.doi.org/10.3109/02688697.2012.717985DOI Listing
April 2013

The Orbit Galaxy XTRASOFT Coils: A Multicenter Study of Coil Safety and Efficacy in Both Ruptured and Unruptured Cerebral Aneurysms.

J Vasc Interv Neurol 2012 Jun;5(1):17-21

Department of Neurosurgery, George Washington University, Washington, DC, USA.

Increase packing density with the use of softer three-dimensional (3D) coils has been indicated in reducing aneurysm recurrence. We are reporting a multicenter initial experience of using the Orbit Galaxy XTRASOFT which is a stretch-resistant, softer 3D coil in both ruptured and unruptured aneurysms. A total of 57 consecutive patients from five high-volume neurointerventional centers were reported where at least one Galaxy XTRASOFT coil was used during a procedure. There were 25 patients with ruptured aneurysm and 32 with elective coiling. The overall complication rate was 3.5%, one patient with nonoperative retroperitoneal hematoma and one patient with intraoperative rupture but with no neurological deficit. The occlusion rate of 90% or greater was achieved in 86% of the cases. The discharge modified Rankin score of 0 or 1 was achieved in 100% of the elective coiling and 65% in the ruptured cases. Early experience with Galaxy XTRASOFT coils for both ruptured and unruptured aneurysms appears to be safe with good aneurysm obliteration and low complication rate.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3379903PMC
June 2012

Intentional partial coiling dome protection of complex ruptured cerebral aneurysms prevents acute rebleeding and produces favorable clinical outcomes.

Acta Neurochir (Wien) 2012 Jan 9;154(1):27-31. Epub 2011 Nov 9.

Department of Neurosurgery, University of Florida, Gainesville, USA.

Background: The coiling of ruptured cerebral aneurysms protects against acute rebleeding; however, whether partially coiling a ruptured cerebral aneurysm protects against acute rebleeding has never been demonstrated.

Objective: This study was performed to test our hypothesis that intentional partial coiling of complex ruptured cerebral aneurysms, which are unfavorable for clipping and cannot be completely coiled primarily, prevents acute rebleeding to allow for clinical and neurological recovery until definitive treatment and produces favorable clinical outcomes.

Methods: Data were collected from the prospective databases of three centers. Only subarachnoid hemorrhage patients that were treated with a strategy of intentional partial coiling for dome protection were included. This did not include patients in whom the goal was complete coiling but only subtotal coil occlusion was achieved.

Results: Fifteen patients [aged 51 ± 13 years; HH 3-5 (n = 7); Fisher 3-4 (n = 9)] were treated with intentional partial dome protection. Aneurysm size was 12.8 ± 5.4 mm; neck size 4.9 ± 3 mm; 12 anterior circulation. Four intentional partial coilings were performed with balloon assistance. Definitive treatment was performed 92 ± 90 days later, with no case of rebleeding. Definitive treatment was clipping (n = 8), stent-coiling (n = 5), Onyx (n = 1), further coiling (n = 1). Clinical outcome was favorable in 13 cases (GOS 4-5), fair in one (GOS 3), and death in one (GOS 1).

Conclusions: Judicious use of a treatment strategy of intentional partial dome protection for complex aneurysms that are not favorable for clipping and in which complete coiling primarily is not possible may prevent acute rebleeding and produce favorable clinical outcomes.
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http://dx.doi.org/10.1007/s00701-011-1214-zDOI Listing
January 2012

Perioperative safety of Hydrosoft coils.

J Neurointerv Surg 2012 Sep 13;4(5):375-8. Epub 2011 Sep 13.

Department of Neurosurgery, University of Florida, Gainesville, FL 32610, USA.

Objective: Hydrosoft coils were developed to serve as finishing coils to prevent aneurysmal recurrence at the neck. Initial animal studies were encouraging since some studies showed endothelial healing across the neck without recurrence over time. However, theoretical concerns exist regarding the potential threat to parent vessels as the Hydrosoft coils at the neck expand, as well as whether such coils can be adequately supple to safely serve as a true finishing coil. A retrospective review of the initial clinical experience utilizing Hydrosoft coils from three high-volume centers was performed.

Methods: Each center was asked to report angiographic (aneurysmal location, aneurysmal maximal size, neck size, incidence of intraprocedural parent vessel thrombosis, coil herniation, aneurysmal rupture as well as Raymond scale and percent occlusion after coiling) and clinical (rupture status, Hunt and Hess grade, incidence of stroke, hemorrhage, vasospasm and hydrocephalus) data on consecutive patients who underwent placement of Hydrosoft coils.

Results: A total of 141 patients were enrolled. Embolization achieved a Raymond scale score of I (complete obliteration) in 79 aneurysms (56%), II (residual neck) in 40 aneurysms (28%) and III (residual dome) in 21 aneurysms (15%); in one case the Hydrosoft coil could not be placed. Procedural morbidity and mortality were 2.1% and 1.4%, respectively. No complications were definitively attributed to the use of Hydrosoft coils. There were three cases (2.1%) of parent vessel thrombosis, two of which resolved after intraprocedural administration of thrombolytic agents and did not lead to neurological sequelae. The incidences of intraprocedural or periprocedural aneurysmal rupture (2.1%), cerebral hemorrhage (3.5%), stroke (4.9%), vasospasm (26.2%) or hydrocephalus (31.1%) were comparable to contemporary literature.

Conclusion: The use of Hydrosoft coils appears to be safe and does not lead to higher complication rates than are currently accepted in the literature. Further prospective studies are required to determine whether the use of Hydrosoft coils results in a lower incidence of aneurysmal recurrence.
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http://dx.doi.org/10.1136/neurintsurg-2011-010106DOI Listing
September 2012