Publications by authors named "Danielle Golub"

18 Publications

  • Page 1 of 1

Iatrogenic haemoperitoneum requiring transfusion after ventriculoperitoneal shunt placement: case report.

Br J Neurosurg 2020 Dec 11:1-4. Epub 2020 Dec 11.

Department of Neurosurgery, New York University School of Medicine, NYU Langone Health, New York, NY, USA.

Cerebrospinal fluid (CSF) diversion for hydrocephalus via ventriculoperitoneal (VP) shunting is one of the most commonly performed neurosurgical procedures. Unfortunately, VP shunting also carries a high complication rate. While long-term complications of VP shunting are generally well-described, the literature on more acute, iatrogenic injury during shunt placement is essentially limited to easily identifiable intracranial bleeds. Herein is presented the first reported case of iatrogenic abdominal wall vessel injury as a consequence of blind distal VP shunt catheter placement causing a critical haemoperitoneum that necessitated multiple transfusions. Presentation and recognition of this bleed was delayed as it occurred over a number of days. Injury to the inferior epigastric artery, or potentially a distal branch of the superficial epigastric artery, is suspected to have occurred during either blind subcutaneous tunnelling of the shunt catheter passage or during penetration of the peritoneum. Haemoperitoneum as a potential complication of procedures involving manipulation or penetration of the abdominal wall (i.e. paracentesis) is well-described in the medical and general surgical literature, and ultrasound-guidance has been widely adopted to mitigate bleeding in these cases. Familiarity with intra-abdominal haemorrhage as a potential complication of VP shunting and an understanding of its presentation is critical for timely identification of this phenomenon. Furthermore, the use of real-time ultrasound-guidance for tunnelling and distal shunt catheter placement may decrease the incidence of intrabdominal complications after shunt placement more generally and should be considered an area of future study.
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http://dx.doi.org/10.1080/02688697.2020.1858025DOI Listing
December 2020

Pediatric midline H3K27M-mutant tumor with disseminated leptomeningeal disease and glioneuronal features: case report and literature review.

Childs Nerv Syst 2020 Sep 28. Epub 2020 Sep 28.

Division of Pediatric Neurosurgery, Department of Neurosurgery, NYU Grossman School of Medicine, NYU Langone Health, New York, NY, USA.

Background: H3K27M-mutant midline lesions were recently reclassified by the World Health Organization (WHO) as "diffuse midline glioma" (DMG) based entirely on their molecular signature. DMG is one of the most common and most lethal pediatric brain tumors; terminal progression is typically caused by local midbrain or brainstem progression, or secondary leptomeningeal dissemination. H3K27M mutations have also been infrequently associated with a histologically and prognostically diverse set of lesions, particularly spinal masses with early leptomeningeal spread.

Case Presentation: A 15-year-old girl after 1 week of symptoms was found to have a T2/FLAIR-hyperintense and contrast-enhancing thalamic mass accompanied by leptomeningeal enhancement along the entire neuraxis. Initial infectious workup was negative, and intracranial biopsy was inconclusive. Spinal arachnoid biopsy revealed an H3K27M-mutant lesion with glioneuronal features, classified thereafter as DMG. She received craniospinal irradiation with a boost to the thalamic lesion. Imaging 1-month post-radiation demonstrated significant treatment response with residual enhancement at the conus.

Conclusions: This case report describes the unique presentation of an H3K27M-mutant midline lesion with significant craniospinal leptomeningeal spread on admission and atypical glioneuronal histopathological markers. With such florid leptomeningeal disease, spinal dural biopsy should be considered earlier given its diagnostic yield in classifying the lesion as DMG. Consistent with similar prior reports, this lesion additionally demonstrated synaptophysin positivity-also potentially consistent with a diagnosis of diffuse leptomeningeal glioneuronal tumor (DLGNT). In atypical DMG cases, particularly with leptomeningeal spread, further consideration of clinical and histopathological context is necessary for accurate diagnosis and prognostication.
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http://dx.doi.org/10.1007/s00381-020-04892-0DOI Listing
September 2020

Benefits of the Subdural Evacuating Port System (SEPS) Procedure Over Traditional Craniotomy for Subdural Hematoma Evacuation.

Neurohospitalist 2020 Oct 4;10(4):257-265. Epub 2020 May 4.

Department of Neurosurgery, NYU School of Medicine, NYU Langone Health, New York, NY, USA.

Background: There remains no consensus on the optimal primary intervention for subdural hematoma (SDH). Although historically favored, craniotomy carries substantial morbidity and incurs significant costs. Contrastingly, the subdural evacuating port system (SEPS) is a minimally invasive bedside procedure. We assessed the benefits of SEPS over traditional craniotomy for SDH evacuation.

Methods: A single-center retrospective cohort study of SDH patients receiving craniotomy or SEPS between 2012 and 2017 was performed. Information regarding demographics, medical history, presentation, surgical outcomes, cost, and complications was collected. Pre- and postoperative hematoma volumes were calculated using 3D image segmentation using Vitrea software. Multivariate regression models were employed to assess the influence of intervention choice.

Results: Of 107 patients, 68 underwent craniotomy and 39 underwent SEPS. There were no differences in age, sex, blood thinner use, platelet count, INR, hematoma lateralization, age, volume, or midline shift at presentation between intervention groups. Although there was no difference in percent residual hematoma volume 24-hour postintervention (44.1% vs 45.1%, = .894), SEPS was associated with lower hospitalization costs ($108 391 vs $166 318, * = .002), shorter length of stay (4.0 vs 5.8 days, * = .0002), and fewer postoperative seizures (2.6% vs 17.7%, * = .048). Reoperation rate was higher after SEPS overall (33.3% vs 13.2%, * = .048) but comparable to craniotomy in chronic SDH (12.50% vs 7.69%, = 1.000).

Conclusion: In this retrospective cohort, SEPS was noninferior to craniotomy at reducing SDH hematoma volume. The SEPS procedure was also associated with decreased length of stay hospitalization costs, and postoperative seizures and demonstrated a comparable recurrence rate to craniotomy for chronic SDH in particular.
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http://dx.doi.org/10.1177/1941874420920520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495698PMC
October 2020

Venous Duplex Ultrasound Surveillance in the Neurosurgical Population: A Single-Center Quality Improvement Initiative.

World Neurosurg 2020 Dec 3;144:e80-e86. Epub 2020 Aug 3.

Department of Neurosurgery, NYU Langone Health, New York, New York, USA. Electronic address:

Background: Venous thromboembolism (VTE) represents a significant source of morbidity and mortality in the inpatient population and is considered a leading preventable cause of death among inpatients. Neurosurgical inpatients are of particular interest because of the greater rates of immobility, steroid use, and potential consequences of postoperative hemorrhage. A consensus protocol for VTE screening in this population has not yet been developed, and institutional protocols vary widely.

Methods: We performed a retrospective review of lower extremity venous duplex ultrasonography (VDUS) usage at our institution and applied this information to the development of a neurosurgery department protocol, with consideration of high-risk patient risk factors and indications for VDUS ordering. We then implemented this protocol, which consisted of preoperative screening of patients at high risk of VTE and limited postoperative surveillance, for a 6-month period and compared VDUS usage and VTE occurrence.

Results: Preoperative VDUS screening before nonemergent neurosurgical procedures in high-risk patients with active cancer, an inability to ambulate, or a history of deep vein thrombosis (DVT) identified proximal DVTs that were then treated. Postoperative routine surveillance VDUS scans only diagnosed incidental isolated calf DVT for which no clinically relevant sequelae occurred. Overall, postoperative surveillance VDUS usage decreased significantly (66.9% vs. 13.5%; P = 0.001).

Conclusions: Our findings lend support to preoperative screening of high-risk patients and suggest that routine postoperative VDUS surveillance of asymptomatic patients is unnecessary.
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http://dx.doi.org/10.1016/j.wneu.2020.07.207DOI Listing
December 2020

Orbital Rosai-Dorfman disease initially diagnosed as IgG4-related disease: a case report.

Acta Neuropathol Commun 2020 07 18;8(1):113. Epub 2020 Jul 18.

Department of Pathology, NYU Grossman School of Medicine, NYU Langone Health, 550 First Ave, MSB 5th Floor, New York, NY, 10016, USA.

Inflammatory orbital lesions include a broad list of diagnoses, many of them with overlapping clinical and radiographic features. They often present a diagnostic conundrum, even to the most experienced orbital specialist, thus placing considerable weight on surgical biopsy and histopathological analysis. However, histopathological diagnosis is also inherently challenging due to the rarity of these lesions and the overlaps in histologic appearance among distinct disease entities. We herein present the case of an adolescent male with a subacutely progressive orbital mass that generated a significant diagnostic dilemma. Early orbital biopsy was consistent with a benign fibro-inflammatory lesion, but corticosteroid therapy was ineffective in halting disease progression. After an initial substantial surgical debulking, histopathological analysis revealed several key features consistent with IgG4-related disease (IgG4-RD), a systemic fibro-inflammatory process typically accompanied by multifocal tumor-like lesions. Surprisingly, within months, there was clear evidence of clinical and radiographic disease progression despite second-line rituximab treatment, prompting a second surgical debulking. This final specimen displayed distinctive features of Rosai-Dorfman disease (RDD), a systemic inflammatory disease characterized by uncontrolled histiocytic proliferation. Interestingly, certain features of this re-excision specimen were still reminiscent of IgG4-RD, which not only reflects the difficulty in differentiating RDD from IgG4-RD in select cases, but also illustrates that these diagnoses may exist along a spectrum that likely reflects a common underlying pathogenetic mechanism. This case emphasizes the importance of surgical biopsy or resection and histopathological analysis in diagnosing-and, ultimately, treating-rare, systemic inflammatory diseases involving the orbit, and, furthermore, highlights the shared histopathological features between RDD and IgG4-RD.
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http://dx.doi.org/10.1186/s40478-020-00995-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368749PMC
July 2020

Expression profiling of the adhesion G protein-coupled receptor GPR133 (ADGRD1) in glioma subtypes.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa053. Epub 2020 Apr 28.

Departments of Neurosurgery, New York, New York, USA.

Background: Glioma is a family of primary brain malignancies with limited treatment options and in need of novel therapies. We previously demonstrated that the adhesion G protein-coupled receptor GPR133 (ADGRD1) is necessary for tumor growth in adult glioblastoma, the most advanced malignancy within the glioma family. However, the expression pattern of GPR133 in other types of adult glioma is unknown.

Methods: We used immunohistochemistry in tumor specimens and non-neoplastic cadaveric brain tissue to profile GPR133 expression in adult gliomas.

Results: We show that GPR133 expression increases as a function of WHO grade and peaks in glioblastoma, where all tumors ubiquitously express it. Importantly, GPR133 is expressed within the tumor bulk, as well as in the brain-infiltrating tumor margin. Furthermore, GPR133 is expressed in both isocitrate dehydrogenase (IDH) wild-type and mutant gliomas, albeit at higher levels in IDH wild-type tumors.

Conclusion: The fact that GPR133 is absent from non-neoplastic brain tissue but de novo expressed in glioma suggests that it may be exploited therapeutically.
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http://dx.doi.org/10.1093/noajnl/vdaa053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262742PMC
April 2020

Earlier radiosurgery leads to better pain relief and less medication usage for trigeminal neuralgia patients: an international multicenter study.

J Neurosurg 2020 Jul 3:1-8. Epub 2020 Jul 3.

1Department of Neurosurgery, New York University Langone Medical Center, New York, New York.

Objective: Trigeminal neuralgia (TN) is a chronic pain condition that is difficult to control with conservative management. Furthermore, disabling medication-related side effects are common. This study examined how stereotactic radiosurgery (SRS) affects pain outcomes and medication dependence based on the latency period between diagnosis and radiosurgery.

Methods: The authors conducted a retrospective analysis of patients with type I TN at 12 Gamma Knife treatment centers. SRS was the primary surgical intervention in all patients. Patient demographics, disease characteristics, treatment plans, medication histories, and outcomes were reviewed.

Results: Overall, 404 patients were included. The mean patient age at SRS was 70 years, and 60% of the population was female. The most common indication for SRS was pain refractory to medications (81%). The median maximum radiation dose was 80 Gy (range 50-95 Gy), and the mean follow-up duration was 32 months. The mean number of medications between baseline (pre-SRS) and the last follow-up decreased from 1.98 to 0.90 (p < 0.0001), respectively, and this significant reduction was observed across all medication categories. Patients who received SRS within 4 years of their initial diagnosis achieved significantly faster pain relief than those who underwent treatment after 4 years (median 21 vs 30 days, p = 0.041). The 90-day pain relief rate for those who received SRS ≤ 4 years after their diagnosis was 83.8% compared with 73.7% in patients who received SRS > 4 years after their diagnosis. The maximum radiation dose was the strongest predictor of a durable pain response (OR 1.091, p = 0.003). Early intervention (OR 1.785, p = 0.007) and higher maximum radiation dose (OR 1.150, p < 0.0001) were also significant predictors of being pain free (a Barrow Neurological Institute pain intensity score of I-IIIA) at the last follow-up visit. New sensory symptoms of any kind were seen in 98 patients (24.3%) after SRS. Higher maximum radiation dose trended toward predicting new sensory deficits but was nonsignificant (p = 0.075).

Conclusions: TN patients managed with SRS within 4 years of diagnosis experienced a shorter interval to pain relief with low risk. SRS also yielded significant decreases in adjunct medication utilization. Radiosurgery should be considered earlier in the course of treatment for TN.
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http://dx.doi.org/10.3171/2020.4.JNS192780DOI Listing
July 2020

Modafinil in Recovery after Stroke (MIRAS): A Retrospective Study.

J Stroke Cerebrovasc Dis 2020 Apr;29(4):104645

NYU Langone Health, Department of Neurology, New York, New York. Electronic address:

Background And Purpose: Acute rehabilitation is known to enhance stroke recovery. However, poststroke lethargy and fatigue can hinder participation in rehabilitation therapies. We hypothesized that in patients with moderate to severe stroke complicated by poststroke fatigue and lethargy early stimulant therapy with modafinil increases favorable discharge disposition defined as transfer to acute inpatient rehabilitation or home.

Methods: We retrospectively reviewed a cohort of patients with acute stroke admitted to the stroke service over a 3-year period. All patients 18 years or older with confirmed ischemic or hemorrhagic stroke, an NIHSS greater than or equal to 5 and documentation of fatigue/lethargy in clinical documentation were included. We compared patients that were treated with modafinil 50-200 mg to those managed with standard care. The primary outcome measure was discharge disposition. Secondary outcome was 90 day modified Rankin score (mRS). Statistical significance was determined using chi-square test for association and logistic regression models. Logistic regression models were derived in 2 ways with both raw data and an adjusted model that accounted for age, sex, and NIHSS score to account for the lack of randomization.

Results: This study included 199 stroke patients (145 ischemic, 54 hemorrhagic). Seventy-two (36.2%) were treated with modafinil and 129 (64.8%) were discharged to acute inpatient rehabilitation, while none were recommended for discharge home. Median NIHSS for modafinil patients was 13.5 versus 11 for standard care patients (P = .059). In adjusted models, modafinil was associated with higher odds of favorable discharge disposition (OR 2.00, 95% CI 1.01-3.95). Favorable outcome at 90 days defined as mRS less than or equal to 2 occurred more frequently with modafinil (5.6% versus 3.3%) but this did not achieve statistical significance (P > .1). These results occurred despite the modafinil group requiring longer ICU stays and having more in-hospital complications such as infections and need for percutaneous gastrostomy tubes. The benefit of modafinil was seen across all subgroups except those with severe stroke (NIHSS ≥ 15). There were no significant adverse events associated with modafinil administration.

Conclusions: Modafinil use in acute in-hospital stroke patients with moderate stroke complicated by lethargy and fatigue was associated with improved discharge disposition. Randomized controlled trials are needed to further study the safety, efficacy, and long-term effects of modafinil in this patient population.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104645DOI Listing
April 2020

Intraoperative MRI versus 5-ALA in high-grade glioma resection: a network meta-analysis.

J Neurosurg 2020 Feb 21:1-15. Epub 2020 Feb 21.

6Departments of Neurosurgery, Otolaryngology, and Neuroscience, Weill Cornell Medicine, NewYork-Presbyterian Hospital, New York, New York; and.

Objective: High-grade gliomas (HGGs) continue to carry poor prognoses, and patient outcomes depend heavily on the extent of resection (EOR). The utility of conventional image-guided surgery is limited by intraoperative brain shift. More recent techniques to maximize EOR, including intraoperative imaging and the use of fluorescent dyes, combat these limitations. However, the relative efficacy of these two techniques has never been systematically compared. Thus, the authors performed an exhaustive systematic review in conjunction with quantitative network meta-analyses to evaluate the comparative effectiveness of 5-aminolevulinic acid (5-ALA) and intraoperative MRI (IMRI) in optimizing EOR in HGG. They secondarily analyzed associated progression-free and overall survival and performed subgroup analyses by level of evidence.

Methods: PubMed, Embase, Cochrane Central, and Web of Science were searched for studies evaluating conventional neuronavigation, IMRI, and 5-ALA in HGG resection. The primary study endpoint was the proportion of patients attaining gross-total resection (GTR), defined as 100% elimination of contrast-enhancing lesion on postoperative MRI. Secondary endpoints included overall and progression-free survival and subgroup analyses for level of evidence. Comparative efficacy analysis of IMRI and 5-ALA was performed using Bayesian network meta-analysis models.

Results: This analysis included 11 studies. In a classic meta-analysis, both IMRI (OR 4.99, 95% CI 2.65-9.39, p < 0.001) and 5-ALA (OR 2.866, 95% CI 2.127-3.863, p < 0.001) were superior to conventional navigation in achieving GTR. Bayesian network analysis was employed to indirectly compare IMRI to 5-ALA, and no significant difference in GTR was found between the two (OR 1.9 favoring IMRI, 95% CI 0.905-3.989, p = 0.090). A handful of studies additionally suggested that the use of either IMRI (2 and 4 studies, respectively) or 5-ALA (2 and 2 studies, respectively) improves progression-free and overall survival.

Conclusions: IMRI and 5-ALA are individually superior to conventional neuronavigation for achieving GTR of HGG. Between IMRI and 5-ALA, neither method is clearly more effective. Future studies evaluating the comparative cost and surgical time associated with IMRI and 5-ALA will better inform any cost-benefit analysis.
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http://dx.doi.org/10.3171/2019.12.JNS191203DOI Listing
February 2020

Possible Abscopal Effect Observed in Frontal Meningioma After Localized IMRT on Posterior Meningioma Resection Cavity Without Adjuvant Immunotherapy.

Front Oncol 2019 18;9:1109. Epub 2019 Oct 18.

Department of Neurosurgery, North Shore University Hospital, Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, United States.

Localized radiation therapy (RT) is known to infrequently cause off-target or "abscopal" effects at distant metastatic lesions. The mechanism through which abscopal effects occur remains unknown, but is thought to be caused by a humoral immune response to tumor-specific antigens generated by RT. Combination treatment regimens involving RT and immunotherapy to boost the humoral immune response have demonstrated synergistic effects in promoting and accelerating abscopal effects in metastatic cancer. Nevertheless, abscopal effects, particularly after RT alone, remain exceedingly rare. We report the case of an 84-year-old man with an atypical meningioma, who demonstrated a radiographically significant response to an untreated second intracranial lesion, likely also a meningioma, after intensity-modulated radiation therapy (IMRT) to a separate, detatched resection cavity. Serial annual MRI imaging starting at 2- to 3.5-year (most recent) post-IMRT follow-up demonstrated a persistent decrease in both tumor size and surrounding edema in the untreated second lesion, suggestive of a possible abscopal effect. We describe here the first report of a potential abscopal effect in meningioma, summarize the limited literature on the topic of abscopal effects in cancer, and detail the existing hypothesis on how this phenomenon may occur and possibly relate to the development of future treatments for patients with metastatic disease.
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http://dx.doi.org/10.3389/fonc.2019.01109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813201PMC
October 2019

Mutant Isocitrate Dehydrogenase Inhibitors as Targeted Cancer Therapeutics.

Front Oncol 2019 17;9:417. Epub 2019 May 17.

Department of Neurosurgery, New York University School of Medicine, NYU Langone Health, New York, NY, United States.

The identification of heterozygous neomorphic isocitrate dehydrogenase (IDH) mutations across multiple cancer types including both solid and hematologic malignancies has revolutionized our understanding of oncogenesis in these malignancies and the potential for targeted therapeutics using small molecule inhibitors. The neomorphic mutation in IDH generates an oncometabolite product, 2-hydroxyglutarate (2HG), which has been linked to the disruption of metabolic and epigenetic mechanisms responsible for cellular differentiation and is likely an early and critical contributor to oncogenesis. In the past 2 years, two mutant IDH (mutIDH) inhibitors, Enasidenib (AG-221), and Ivosidenib (AG-120), have been FDA-approved for IDH-mutant relapsed or refractory acute myeloid leukemia (AML) based on phase 1 safety and efficacy data and continue to be studied in trials in hematologic malignancies, as well as in glioma, cholangiocarcinoma, and chondrosarcoma. In this review, we will summarize the molecular pathways and oncogenic consequences associated with mutIDH with a particular emphasis on glioma and AML, and systematically review the development and preclinical testing of mutIDH inhibitors. Existing clinical data in both hematologic and solid tumors will likewise be reviewed followed by a discussion on the potential limitations of mutIDH inhibitor monotherapy and potential routes for treatment optimization using combination therapy.
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http://dx.doi.org/10.3389/fonc.2019.00417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534082PMC
May 2019

A Longitudinally Extensive Spinal Cord Lesion Restricted to Gray Matter in an Adolescent Male.

Front Neurol 2019 20;10:270. Epub 2019 Mar 20.

Department of Pediatrics, New York University School of Medicine, New York, NY, United States.

Longitudinally extensive spinal cord lesions (LECL) restricted to gray matter are poorly understood as are their neurodevelopmental repercussions in children. We herein report the critical case of a 13-year-old male presenting with progressive quadriparesis found to have cervical LECL restricted to the anterior horns. Challenged with a rare diagnostic dilemma, the clinical team systematically worked through potential vascular, genetic, infectious, rheumatologic, and paraneoplastic diagnoses before assigning a working diagnosis of acute inflammatory myelopathy. Nuanced consideration of and workup for both potential ischemic causes (arterial dissection, fibrocartilaginous embolism, vascular malformation) and specific inflammatory conditions including Transverse Myelitis, Neuromyelitis Optica Spectrum Disorders (NMOSD), Multiple Sclerosis (MS), Acute Disseminated Encephalomyelitis (ADEM), and Acute Flaccid Myelitis (AFM) is explained in the context of a comprehensive systematic review of the literature on previous reports of gray matter-restricted longitudinally extensive cord lesions in children. Treatment strategy was ultimately based on additional literature review of treatment-refractory acute inflammatory neurological syndromes in children. A combination of high-dose steroids and plasmapheresis was employed with significant improvement in functional outcome, suggesting a potential benefit of combination immune-modulatory treatment in these patients. This case furthermore highlights quality clinical reasoning with respect to the elusive nature of diagnosis, nuances in neuroimaging, and multifocal treatment strategies in pediatric LECL.
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http://dx.doi.org/10.3389/fneur.2019.00270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435483PMC
March 2019

Spontaneous bilateral internal carotid and vertebral artery dissections with dominant-hemisphere circulation maintained by external carotid artery-ophthalmic artery anastomoses.

Neurosurg Focus 2019 02;46(2):E6

3Department of Radiology, and.

Spontaneous cervical artery dissection (sCAD) is a major cause of stroke in young adults. Multiple sCAD is a rarer, more poorly understood presentation of sCAD that has been increasingly attributed to cervical trauma such as spinal manipulation or genetic polymorphisms in extracellular matrix components. The authors present the case of a 49-year-old, otherwise healthy woman, who over the course of 2 weeks developed progressive, hemodynamically significant, bilateral internal carotid artery and vertebral artery dissections. Collateral response involved extensive external carotid artery-internal carotid artery anastomoses via the ophthalmic artery, which were instrumental in maintaining perfusion because circle of Willis and leptomeningeal anastomotic responses were hampered by the dissection burden in the corresponding collateral vessels. Endovascular intervention by placement of Pipeline embolization devices and Atlas stents in bilateral internal carotid arteries was successfully performed. No syndromic or systemic etiology was discovered during a thorough workup.
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http://dx.doi.org/10.3171/2018.11.FOCUS18443DOI Listing
February 2019

Supracerebellar Transtentorial Approach for Occipital Meningioma to Maximize Visual Preservation: Technical Note.

Oper Neurosurg (Hagerstown) 2019 10;17(4):E177-E183

Department of Neurosurgery, North Shore University Hospital, Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York.

Background And Importance: Surgery for resection of tentorial meningiomas compressing primary visual cortex carries a significant risk of worsening vision. This concern is especially acute in patients with a preexisting visual deficit. Approaches that involve mechanical retraction of the occipital lobe further threaten visual function. The supracerebellar transtentorial (SCTT) approach, which does not carry a risk of occipital retraction injury, should be considered for patients with occipital tentorial meningiomas to maximize functional visual outcomes.

Clinical Presentation: A 54-yr-old woman underwent 2 resections and radiation therapy for a right occipital oligodendroglioma as a teenager. She was left with a complete left homonymous hemianopsia. The patient now presented with progressive vision loss in her remaining right visual field. Imaging revealed a left occipital superiorly projecting tentorial meningioma. To preserve her remaining visual function the SCTT approach was chosen for resection. A Simpson grade 1 removal was achieved without disrupting the occipital lobe pia or requiring mechanical cerebellar retraction. A diagnosis of a WHO grade II meningioma (presumably radiation induced) was made. The patient's vision returned to premorbid baseline 1 wk after surgery.

Conclusion: The SCTT approach should be considered for the surgical management of patients with occipital tentorial meningiomas when visual preservation is at risk. This approach avoids transgression of visual cortex and minimizes the risk of venous infarction or contusions from retraction injury.
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http://dx.doi.org/10.1093/ons/opy380DOI Listing
October 2019

Antipsychotics in Hyperthyroid-Related Psychosis: Case Report and Systematic Review.

Neuro Endocrinol Lett 2018 Mar;39(1):65-74

Department of Psychiatry, NYU School of Medicine, 550 1st Avenue, New York, NY, 10016, USA.

Objectives: Hyperthyroidism has been associated with relatively rare presentations of psychotic symptoms. We report an example of the successful use of antipsychotics to manage psychotic symptoms in hyperthyroid-related psychosis. Furthermore, we systematically describe the available literature on the use of antipsychotics in this setting to determine the associated relative efficacies of the various antipsychotic agents.

Methods: Presentation of a case of hyperthyroid-related psychosis treated with an antipsychotic agent followed by a systematic review of all similar cases: PubMed, Ovid MEDLINE and PMC were searched for articles published between 1960 and 2017 that report on the use of specific antipsychotics in the management of hyperthyroid-related psychosis.

Results: An 81-year-old woman presented with hallucinations and delusions in the context of untreated Graves' Disease and was effectively treated with medical management of her thyroidopathy and psychopharmacologic management of psychotic symptoms. Systematic review revealed that typical and atypical antipsychotics have comparable efficacy in the management of psychotic symptoms in hyperthyroid-related psychosis.

Conclusion: Choice of antipsychotic in hyperthyroid-related psychosis should be primarily based on side-effect profile and medical comorbidities. Risperidone is the optimal and seemingly effective choice for treating hyperthyroid-related psychosis in an elderly thyrotoxic patient.
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March 2018

Modeling Glioma with Human Embryonic Stem Cell-Derived Neural Lineages.

Methods Mol Biol 2018 ;1741:227-237

Department of Neurosurgery, NYU School of Medicine, New York, NY, USA.

Gliomas are malignant primary tumors of the central nervous system. Their cell-of-origin is thought to be a neural progenitor or stem cell that acquires mutations leading to oncogenic transformation. Thanks to advances in human stem cell biology, it has become possible to derive human cell types that represent putative cells-of-origin in vitro and model the gliomagenesis process by systematically introducing genetic alterations in these human cells. Here, we present methods to derive human neural stem cells (NSCs) from human embryonic stem cells (hESCs). Because these NSCs are genetically unmodified at baseline, they can be used as a cellular platform to study the effects of individual oncogenic hits in a well-controlled manner in the backdrop of a human genetic background. We also present some key applications of these NSCs, which include their transduction with lentiviral vectors, their neuroglial differentiation and xenografting methods into immunocompromised mice to assess in vivo behavior.
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http://dx.doi.org/10.1007/978-1-4939-7659-1_19DOI Listing
December 2018

Low-Grade Astrocytoma Mutations in IDH1, P53, and ATRX Cooperate to Block Differentiation of Human Neural Stem Cells via Repression of SOX2.

Cell Rep 2017 Oct;21(5):1267-1280

Department of Neurosurgery, NYU School of Medicine, New York, NY 10016, USA; Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA; Brain Tumor Center, NYU School of Medicine, New York, NY 10016, USA; Neuroscience Institute, NYU School of Medicine, New York, NY 10016, USA. Electronic address:

Low-grade astrocytomas (LGAs) carry neomorphic mutations in isocitrate dehydrogenase (IDH) concurrently with P53 and ATRX loss. To model LGA formation, we introduced R132H IDH1, P53 shRNA, and ATRX shRNA into human neural stem cells (NSCs). These oncogenic hits blocked NSC differentiation, increased invasiveness in vivo, and led to a DNA methylation and transcriptional profile resembling IDH1 mutant human LGAs. The differentiation block was caused by transcriptional silencing of the transcription factor SOX2 secondary to disassociation of its promoter from a putative enhancer. This occurred because of reduced binding of the chromatin organizer CTCF to its DNA motifs and disrupted chromatin looping. Our human model of IDH mutant LGA formation implicates impaired NSC differentiation because of repression of SOX2 as an early driver of gliomagenesis.
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http://dx.doi.org/10.1016/j.celrep.2017.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687844PMC
October 2017

Peptide YY signaling in the lateral parabrachial nucleus increases food intake through the Y1 receptor.

Am J Physiol Endocrinol Metab 2015 Oct 1;309(8):E759-66. Epub 2015 Sep 1.

Department of Psychology, University of Pennsylvania, Philadelphia, Pennsylvania; and.

Although central PYY delivery potently increases food intake, the sites of action and mechanisms mediating these hyperphagic effects are not fully understood. The present studies investigate the contribution of lateral parabrachial nucleus (lPBN) PYY-Y receptor signaling to food intake control, as lPBN neurons express Y receptors and receive PYY fibers and are known to integrate circulating and visceral sensory signals to regulate energy balance. Immunohistochemical results identified a subpopulation of gigantocellular reticular nucleus PYY-producing neurons that project monosynaptically to the lPBN, providing an endogenous source of PYY to the lPBN. lPBN microinjection of PYY-(1-36) or PYY-(3-36) markedly increased food intake by increasing meal size. To determine which receptors mediate these behavioral results, we first performed quantitative real-time PCR to examine the relative levels of Y receptor expression in lPBN tissue. Gene expression analyses revealed that, while Y1, Y2, and Y5 receptors are each expressed in lPBN tissue, Y1 receptor mRNA is expressed at fivefold higher levels than the others. Furthermore, behavioral/pharmacological results demonstrated that the hyperphagic effects of PYY-(3-36) were eliminated by lPBN pretreatment with a selective Y1 receptor antagonist. Together, these results highlight the lPBN as a novel site of action for the intake-stimulatory effects of central PYY-Y1 receptor signaling.
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http://dx.doi.org/10.1152/ajpendo.00346.2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609877PMC
October 2015