Jennifer was born and raised in New York and received her undergraduate degree in neuroscience from New York University. Her interest in the neurosciences continued as she completed medical school at Yale School of Medicine. During medical school she spent a year as a Howard Hughes Medical Institute research fellow working on an induced pluripotent stem cell model for congenital brain malformations. Jennifer has a particular interest in improving the quality and effectiveness of patient care, especially for pediatric neurosurgical patients. Under Dr. Kristen Yeom’s group at Stanford, Jennifer is using machine learning to develop automated intraoperative navigation and to improve patient outcomes. Outside of neurosurgery, Jennifer enjoys traveling, trying new food, and spending time with friends and family.
M.H.S., Yale School of Medicine, Health Sciences (2015)
M.D., Yale School of Medicine (2015)
B.S., New York University, Neural Science (Honors) (2010)
Deep Learning for Pediatric Posterior Fossa Tumor Detection and Classification: A Multi-Institutional Study.
AJNR. American journal of neuroradiology
Posterior fossa tumors are the most common pediatric brain tumors. MR imaging is key to tumor detection, diagnosis, and therapy guidance. We sought to develop an MR imaging-based deep learning model for posterior fossa tumor detection and tumor pathology classification.The study cohort comprised 617 children (median age, 92 months; 56% males) from 5 pediatric institutions with posterior fossa tumors: diffuse midline glioma of the pons (n = 122), medulloblastoma (n = 272), pilocytic astrocytoma (n = 135), and ependymoma (n = 88). There were 199 controls. Tumor histology served as ground truth except for diffuse midline glioma of the pons, which was primarily diagnosed by MR imaging. A modified ResNeXt-50-32x4d architecture served as the backbone for a multitask classifier model, using T2-weighted MRIs as input to detect the presence of tumor and predict tumor class. Deep learning model performance was compared against that of 4 radiologists.Model tumor detection accuracy exceeded an AUROC of 0.99 and was similar to that of 4 radiologists. Model tumor classification accuracy was 92% with an F1 score of 0.80. The model was most accurate at predicting diffuse midline glioma of the pons, followed by pilocytic astrocytoma and medulloblastoma. Ependymoma prediction was the least accurate. Tumor type classification accuracy and F1 score were higher than those of 2 of the 4 radiologists.We present a multi-institutional deep learning model for pediatric posterior fossa tumor detection and classification with the potential to augment and improve the accuracy of radiologic diagnosis.
View details for DOI 10.3174/ajnr.A6704
View details for PubMedID 32816765
Deep Learning for Automated Delineation of Pediatric Cerebral Arteries on Pre-operative Brain Magnetic Resonance Imaging
Frontiers in Surgery
View details for DOI 10.3389/fsurg.2020.517375
Age-dependent Intracranial Artery Morphology in Healthy Children.
PURPOSE: Evaluation of intracranial artery morphology plays an important role in diagnosing avariety of neurovascular diseases. In addition to clinical symptoms, diagnosis currently relies on qualitative rather than quantitative evaluation of vascular imaging sequences, such as magnetic resonance angiography (MRA). However, there is a paucity of literature on normal arterial morphology in the pediatric population across brain development. We aimed to quantitatively assess normal, age-related changes in artery morphology in children.METHODS: We performed retrospective analysis of pediatric MRA data obtained from atertiary referral center. An MRA dataset from 98children (49boys/49girls) aged 0.6-20years (median =11.5years) with normal intracranial vasculature was retrospectively collected between 2011 and 2018. All arteries were automatically segmented to determine the vessel radius. Using an atlas-based approach, the average radius and density of arteries were measured in the three main cerebral vascular territories and the radius of five major arteries was determined at corresponding locations.RESULTS: The radii of the major arteries as well as the average artery radius and density in the different vascular territories in the brain remained constant throughout childhood and adolescence (|r| <0.369 in all cases).CONCLUSION: This study presents the first automated evaluation of intracranial vessel morphology on MRA across childhood. Our results can serve as aframework for quantitative evaluation of cerebral vessel morphology in the setting of pediatric neurovascular diseases.
View details for DOI 10.1007/s00062-021-01071-9
View details for PubMedID 34427700
Early Effects of COVID-19 Pandemic on Neurosurgical Training in the United States: A Case Volume Analysis of Eight Programs.
OBJECTIVE: The objective was to determine the impact of the COVID-19 pandemic on operative case volume in 8 US neurosurgical residency training programs in early 2020 and to survey these programs regarding training activities during this period.METHODS: A retrospective review was conducted of monthly operative case volumes and types for 8 residency programs for 2019 and January-April 2020. Cases were grouped as elective cranial, elective spine, and non-elective emergent cases. Programs were surveyed regarding residents' perceptions of the impact of COVID-19 on surgical training, didactics, and research participation. Data was analyzed for individual programs and pooled across programs.RESULTS: Across programs, the 2019 monthly case average was 211 (SD ± 82); 2020 average case volumes for January, February, March, and April were 228±93, 214±84, 180±73, and 107±45, respectively. Compared with 2019, March and April 2020 average cases declined 15% (p=0.003) and 49% (p=0.002), respectively. COVID-19 affected surgical case volume for all programs; 75% reported didactics negatively affected, and 90% reported COVID-19 resulted in increased research time. Several neurosurgery residents have required COVID-19 testing, however, to our knowledge, only one resident from the participating programs tested positive.CONCLUSIONS: This study documents a significant reduction in operative volume in 8 neurosurgery residency training programs in early 2020. During this time, neurosurgery residents engaged in online didactics and research-related activities, reporting increased research productivity. Residency programs should collect data to determine the educational impact of the pandemic on resident operative case volumes, identify deficiencies, and develop plans to mitigate any effects.
View details for DOI 10.1016/j.wneu.2020.10.016
View details for PubMedID 33065350
Commentary: Molecular Diagnosis of Craniosynostosis Using Targeted Next-Generation Sequencing
2020; 87 (2): E108–E109
View details for Web of Science ID 000593120500009
- In Reply: Early Diffusion Magnetic Resonance Imaging Changes in Normal-Appearing Brain in Pediatric Moyamoya Disease. Neurosurgery 2020
Artificial intelligence for automatic cerebral ventricle segmentation and volume calculation: a clinical tool for the evaluation of pediatric hydrocephalus.
Journal of neurosurgery. Pediatrics
Imaging evaluation of the cerebral ventricles is important for clinical decision-making in pediatric hydrocephalus. Although quantitative measurements of ventricular size, over time, can facilitate objective comparison, automated tools for calculating ventricular volume are not structured for clinical use. The authors aimed to develop a fully automated deep learning (DL) model for pediatric cerebral ventricle segmentation and volume calculation for widespread clinical implementation across multiple hospitals.The study cohort consisted of 200 children with obstructive hydrocephalus from four pediatric hospitals, along with 199 controls. Manual ventricle segmentation and volume calculation values served as "ground truth" data. An encoder-decoder convolutional neural network architecture, in which T2-weighted MR images were used as input, automatically delineated the ventricles and output volumetric measurements. On a held-out test set, segmentation accuracy was assessed using the Dice similarity coefficient (0 to 1) and volume calculation was assessed using linear regression. Model generalizability was evaluated on an external MRI data set from a fifth hospital. The DL model performance was compared against FreeSurfer research segmentation software.Model segmentation performed with an overall Dice score of 0.901 (0.946 in hydrocephalus, 0.856 in controls). The model generalized to external MR images from a fifth pediatric hospital with a Dice score of 0.926. The model was more accurate than FreeSurfer, with faster operating times (1.48 seconds per scan).The authors present a DL model for automatic ventricle segmentation and volume calculation that is more accurate and rapid than currently available methods. With near-immediate volumetric output and reliable performance across institutional scanner types, this model can be adapted to the real-time clinical evaluation of hydrocephalus and improve clinician workflow.
View details for DOI 10.3171/2020.6.PEDS20251
View details for PubMedID 33260138
Mortality prediction and long-term outcomes for civilian cerebral gunshot wounds: A decision-tree algorithm based on a single trauma center.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia
Gunshot wounds (GSW) are one of the most lethal forms of head trauma. The lack of clear guidelines for civilian GSW complicates surgical management. We aimed to develop a decision-tree algorithm for mortality prediction and report long-term outcomes on survivors based on 15-year data from our level 1 trauma center. We retrospectively reviewed 96 consecutive patients who presented with cerebral GSWs between 2003 and 2018. Clinical information from our trauma database, EMR, and relevant imaging scans was reviewed. A decision-tree model was constructed based on variables showing significant differences between survivors and non-survivors. After excluding patients who died at arrival, 54 patients with radiologically confirmed intracranial injury were included. Compared to survivors (51.9%), non-survivors (48.1%) were significantly more likely to have perforating (entry and exit wound), as opposed to penetrating (entry wound only), injuries. Bi-hemispheric and posterior fossa involvement, cerebral herniation, and intraventricular hemorrhage were more commonly present in non-survivors. Based on the decision-tree, Glasgow Coma Scale (GCS) > 8 and penetrating, uni-hemispheric injury predicted survival. Among patients with GCS ≤ 8 and normal pupillary response, lack of 1) posterior fossa involvement, 2) cerebral herniation, 3) bi-hemispheric injury, and 4) intraventricular hemorrhage, were associated with survival. Favorable long-term outcomes (mean follow-up 34.4 months) were possible for survivors who required neurosurgery and stable patients who were conservatively managed. We applied clinical and radiological characteristics that predicted survival to construct a decision-tree to facilitate surgical decision-making for GSW. Further validation of the algorithm in a large patient setting is recommended.
View details for DOI 10.1016/j.jocn.2020.03.027
View details for PubMedID 32241644
- Commentary: Molecular Diagnosis of Craniosynostosis Using Targeted Next-Generation Sequencing. Neurosurgery 2019
Diffusion tensor magnetic resonance imaging of the optic nerves in pediatric hydrocephalus.
2019; 47 (6): E16
OBJECTIVE: While conventional imaging can readily identify ventricular enlargement in hydrocephalus, structural changes that underlie microscopic tissue injury might be more difficult to capture. MRI-based diffusion tensor imaging (DTI) uses properties of water motion to uncover changes in the tissue microenvironment. The authors hypothesized that DTI can identify alterations in optic nerve microstructure in children with hydrocephalus.METHODS: The authors retrospectively reviewed 21 children (< 18 years old) who underwent DTI before and after neurosurgical intervention for acute obstructive hydrocephalus from posterior fossa tumors. Their optic nerve quantitative DTI metrics of mean diffusivity (MD) and fractional anisotropy (FA) were compared to those of 21 age-matched healthy controls.RESULTS: Patients with hydrocephalus had increased MD and decreased FA in bilateral optic nerves, compared to controls (p < 0.001). Normalization of bilateral optic nerve MD and FA on short-term follow-up (median 1 day) after neurosurgical intervention was observed, as was near-complete recovery of MD on long-term follow-up (median 1.8 years).CONCLUSIONS: DTI was used to demonstrate reversible alterations of optic nerve microstructure in children presenting acutely with obstructive hydrocephalus. Alterations in optic nerve MD and FA returned to near-normal levels on short- and long-term follow-up, suggesting that surgical intervention can restore optic nerve tissue microstructure. This technique is a safe, noninvasive imaging tool that quantifies alterations of neural tissue, with a potential role for evaluation of pediatric hydrocephalus.
View details for DOI 10.3171/2019.9.FOCUS19619
View details for PubMedID 31786546
- Commentary: Characteristics and Long-Term Outcome of 20 Children With Intramedullary Spinal Cord Cavernous Malformations. Neurosurgery 2019
Early Diffusion Magnetic Resonance Imaging Changes in Normal-Appearing Brain in Pediatric Moyamoya Disease.
BACKGROUND: Moyamoya disease often leads to ischemic strokes visible on diffusion-weighted imaging (DWI) and T2-weighted magnetic resonance imaging (MRI) with subsequent cognitive impairment. In adults with moyamoya, apparent diffusion coefficient (ADC) is correlated with regions of steal phenomenon and executive dysfunction prior to white matter changes.OBJECTIVE: To investigate quantitative global diffusion changes in pediatric moyamoya patients prior to explicit structural ischemic damage.METHODS: We retrospectively reviewed children (<20 yr old) with moyamoya disease and syndrome who underwent bypass surgery at our institution. We identified 29 children with normal structural preoperative MRI and without findings of cortical infarction or chronic white matter ischemic changes. DWI datasets were used to calculate ADC maps for each subject as well as for 60 age-matched healthy controls. Using an atlas-based approach, the cerebral white matter, cerebral cortex, thalamus, caudate, putamen, pallidum, hippocampus, amygdala, nucleus accumbens, and brainstem were segmented in each DWI dataset and used to calculate regional volumes and ADC values.RESULTS: Multivariate analysis of covariance using the regional ADC and volume values as dependent variables and age and gender as covariates revealed a significant difference between the groups (P<.001). Post hoc analysis demonstrated significantly elevated ADC values for children with moyamoya in the cerebral cortex, white matter, caudate, putamen, and nucleus accumbens. No significant volume differences were found.CONCLUSION: Prior to having bypass surgery, and in the absence of imaging evidence of ischemic stroke, children with moyamoya exhibit cerebral diffusion changes. These findings could reflect microstructural changes stemming from exhaustion of cerebrovascular reserve.
View details for DOI 10.1093/neuros/nyz230
View details for PubMedID 31245817
One Hundred Years of Innovation: Automatic Detection of Brain Ventricular Volume using Deep Learning in a Large-Scale Multi-Institutional Study
LIPPINCOTT WILLIAMS & WILKINS. 2019
View details for Web of Science ID 000475965905285
- Arterial spin-labeling cerebral perfusion changes after revascularization surgery in pediatric moyamoya disease and syndrome JOURNAL OF NEUROSURGERY-PEDIATRICS 2019; 23 (4): 486–92
- Commentary: Limited Dorsal Myeloschisis: Reconsideration of its Embryological Origin. Neurosurgery 2019
Transnasal endoscopic approach for pediatric skull base lesions: a case series.
Journal of neurosurgery. Pediatrics
Transnasal endoscopic transsphenoidal approaches constitute an essential technique for the resection of skull base tumors in adults. However, in the pediatric population, sellar and suprasellar lesions have historically been treated by craniotomy. Transnasal endoscopic approaches are less invasive and thus may be preferable to craniotomy, especially in children. In this case series, the authors present their institutional experience with transnasal endoscopic transsphenoidal approaches for pediatric skull base tumors.The authors retrospectively reviewed pediatric patients (age ≤ 18 years) who had undergone transnasal endoscopic transsphenoidal approaches for either biopsy or resection of sellar or suprasellar lesions between 2007 and 2016. All operations were performed jointly by a team of pediatric neurosurgeons and skull base otolaryngologists, except for 8 cases performed by one neurosurgeon.The series included 42 patients between 4 and 18 years old (average 12.5 years) who underwent 51 operations. Headache (45%), visual symptoms (69%), and symptoms related to hormonal abnormalities (71%) were the predominant presenting symptoms. Improvement in preoperative symptoms was seen in 92% of cases. Most patients had craniopharyngiomas (n = 16), followed by pituitary adenomas (n = 12), Rathke cleft cysts (n = 4), germinomas (n = 4), chordomas (n = 2), and other lesion subtypes (n = 4). Lesions ranged from 0.3 to 6.2 cm (median 2.5 cm) in their greatest dimension. Gross-total resection was primarily performed (63% of cases), with 5 subsequent recurrences. Nasoseptal flaps were used in 47% of cases, fat grafts in 37%, and lumbar drains in 47%. CSF space was entered intraoperatively in 15 cases, and postoperative CSF was observed only in lesions with suprasellar extension. There were 8 cases of new hormonal deficits and 3 cases of new cranial nerve deficits. Length of hospital stay ranged from 1 to 61 days (median 5 days). Patients were clinically followed up for a median of 46 months (range 1-120 months), accompanied by a median radiological follow-up period of 45 months (range 3.8-120 months). Most patients (76%) were offered adjuvant therapy.In this single-institution report of the transnasal endoscopic transsphenoidal approach, the authors demonstrated that this technique is generally safe and effective for different types of pediatric skull base lesions. Favorable effects of surgery were sustained during a follow-up period of 4 years. Further refinement in technology will allow for more widespread use in the pediatric population.
View details for DOI 10.3171/2019.4.PEDS18693
View details for PubMedID 31200365
- Deep Brain Stimulation for Pediatric Neuropsychiatric Disorders NEUROTECHNOLOGY AND BRAIN STIMULATION IN PEDIATRIC PSYCHIATRIC AND NEURODEVELOPMENTAL DISORDERS 2019: 237–52
Arterial spin-labeling cerebral perfusion changes after revascularization surgery in pediatric moyamoya disease and syndrome.
Journal of neurosurgery. Pediatrics
OBJECTIVEMoyamoya disease is a dynamic cerebrovascular condition that often requires vascular surveillance. Arterial spin labeling (ASL) is an MR perfusion method that is increasingly used for stroke and other various neurovascular pathologies. Unlike perfusion-weighted MRI, ASL uses endogenous water molecules for signal and therefore obviates gadolinium use; and provides direct, not relative, quantitative cerebral blood flow (CBF) measures. Presently, the potential role of ASL for evaluating postoperative pediatric moyamoya patients is relatively unexplored. This study investigated the role for ASL in evaluating cerebral hemodynamic changes in children who underwent revascularization surgery.METHODSThis retrospective study examined 15 consecutive pediatric patients with moyamoya disease (n = 7) or moyamoya syndrome (n = 8) presenting between 2010 and 2014 who underwent revascularization and in whom 3T ASL was performed pre- and postoperatively. Postoperative MRI at least 3 months after revascularization procedure was used for analysis. Quantitative CBF in various vascular territories was interrogated: anterior, middle, and posterior cerebral arteries, and basal ganglia supplied by the lenticulostriate collaterals, resulting in evaluation of 20 brain regions.RESULTSAfter revascularization, CBF in the high middle cerebral artery territory significantly increased (p = 0.0059), accompanied by a decrease in CBF to the ipsilateral lenticulostriate-supplied basal ganglia (p = 0.0053). No perfusion changes occurred in the remaining cerebral vascular territories after surgery.CONCLUSIONSASL-based quantitative CBF showed improved cerebral perfusion to the middle cerebral artery territory after revascularization in children with both moyamoya syndrome and disease. Reduced perfusion to the basal ganglia might reflect pruning of the lenticulostriate collaterals, potentially from effects of revascularization. ASL can quantitatively evaluate hemodynamic changes in children with moyamoya after revascularization, and it may be a useful adjunct to routine clinical MRI surveillance.
View details for PubMedID 30738390
- Commentary: Optimizing Postoperative Surveillance of Pediatric Low-Grade Glioma Using Tumor Behavior Patterns. Neurosurgery 2019
Traumatic brain injury among female veterans: a review of sex differences in military neurosurgery
2018; 45 (6): E16
The impact of traumatic brain injury (TBI) has been demonstrated in various studies with respect to prevalence, morbidity, and mortality data. Many of the patients burdened with long-term sequelae of TBI are veterans. Although fewer in number, female veterans with TBI have been suggested to suffer from unique physical, mental, and social challenges. However, there remains a significant knowledge gap in the sex differences in TBI. Increased female representation in the military heralds an increased risk of TBI for female soldiers, and medical professionals must be prepared to address the unique health challenges in the face of changing demographics among the veteran TBI population. In this review, the authors aimed to present the current understanding of sex differences in TBI in the veteran population and suggest directions for future investigations.
View details for PubMedID 30544324
Long-term Supratentorial Radiological Effects of Surgery and Local Radiation in Children with Infratentorial Ependymoma.
OBJECT: Current standard of care for children with infratentorial ependymoma includes maximal safe resection and local radiation of 54-59gy. High-dose local radiation has been associated with declines in multiple cognitive domains. The anatomic and physiologic correlates of this cognitive decline remain undefined and there have been no radiographic studies on the long-term effects of this treatment paradigm.METHODS: A comprehensive database of pediatric brain tumor patients treated at Stanford Children's from 2004-2016 was queried. Seven patients with posterior fossa ependymoma were identified who were treated with surgery and local radiation alone, who had no evidence of recurrent disease, and had imaging suitable for analysis. Diffusion-weighted MRI (DWI) datasets were used to calculate apparent diffusion coefficient (ADC) maps for each subject, while arterial spin labeling (ASL) datasets were used to calculated maps of cerebral blood flow (CBF). DWI and ASL datasets of 52 age-matched healthy children were a analyzed in the same fashion to enable group comparisons.RESULTS: Several statistically significant differences were detected between the two groups. CBF was lower in the caudate and pallidum and higher in the nucleus accumbens in the ependymoma cohort compared to controls. ADC was increased in the thalamus and trended towards decreased in the amygdala.CONCLUSIONS: Surgery and local radiation for posterior fossa ependymoma are associated with supratentorial ADC and CBF alterations, which may represent an anatomic and physiologic correlate to the previously published decline in neurocognitive outcomes in this population.
View details for PubMedID 30448581
Rapid-sequence brain magnetic resonance imaging for Chiari I abnormality
JOURNAL OF NEUROSURGERY-PEDIATRICS
2018; 22 (2): 158–64
OBJECTIVE Fast magnetic resonance imaging (fsMRI) sequences are single-shot spin echo images with fast acquisition times that have replaced CT scans for many conditions. Introduced as a means of evaluating children with hydrocephalus and macrocephaly, these sequences reduce the need for anesthesia and can be more cost-effective, especially for children who require multiple surveillance scans. However, the role of fsMRI has yet to be investigated in evaluating the posterior fossa in patients with Chiari I abnormality (CM-I). The goal of this study was to examine the diagnostic performance of fsMRI in evaluating the cerebellar tonsils in comparison to conventional MRI. METHODS The authors performed a retrospective analysis of 18 pediatric patients with a confirmed diagnosis of CM-I based on gold-standard conventional brain MRI and 30 controls without CM-I who had presented with various neurosurgical conditions. The CM-I patients were included if fsMRI studies had been obtained within 1 year of conventional MRI with no surgical intervention between the studies. Two neuroradiologists reviewed the studies in a blinded fashion to determine the diagnostic performance of fsMRI in detecting CM-I. For the CM-I cohort, the fsMRI and T2-weighted MRI exams were randomized, and the blinded reviewers performed tonsillar measurements on both scans. RESULTS The mean age of the CM-I cohort was 7.39 years, and 50% of these subjects were male. The mean time interval between fsMRI and conventional T2-weighted MRI was 97.8 days. Forty-four percent of the subjects had undergone imaging after posterior fossa decompression. The sensitivity and specificity of fsMRI in detecting CM-I was 100% (95% CI 71.51%-100%) and 92.11% (95% CI 78.62%-98.34%), respectively. If only preoperative patients are considered, both sensitivity and specificity increase to 100%. The authors also performed a cost analysis and determined that fsMRI was significantly cost-effective compared to T2-weighted MRI or CT. CONCLUSIONS Despite known limitations, fsMRI may serve as a useful diagnostic and surveillance tool for CM-I. It is more cost-effective than full conventional brain MRI and decreases the need for sedation in young children.
View details for PubMedID 29749883
Conus Medullaris Dural Arteriovenous Fistula Arising From the Artery of the Filum Terminale: 2-Dimensional Operative Video.
Operative neurosurgery (Hagerstown, Md.)
View details for PubMedID 29444295
- Quality of Care and Outcomes in Pediatric Neurosurgery: Incorporating Evidence-Based Practice QUALITY AND SAFETY IN NEUROSURGERY 2018: 237–50
- Outcomes After Endoscopic Endonasal Resection of Craniopharyngiomas in the Pediatric Population WORLD NEUROSURGERY 2017; 108: 6–14
Disruptions in asymmetric centrosome inheritance and WDR62-Aurora kinase B interactions in primary microcephaly
Recessive mutations in WD repeat domain 62 (WDR62) cause microcephaly and a wide spectrum of severe brain malformations. Disruption of the mouse ortholog results in microcephaly underlain by reduced proliferation of neocortical progenitors during late neurogenesis, abnormalities in asymmetric centrosome inheritance leading to neuronal migration delays, and altered neuronal differentiation. Spindle pole localization of WDR62 and mitotic progression are defective in patient-derived fibroblasts, which, similar to mouse neocortical progenitors, transiently arrest at prometaphase. Expression of WDR62 is closely correlated with components of the chromosome passenger complex (CPC), a key regulator of mitosis. Wild type WDR62, but not disease-associated mutant forms, interacts with the CPC core enzyme Aurora kinase B and staining of CPC components at centromeres is altered in patient-derived fibroblasts. Our findings demonstrate critical and diverse functions of WDR62 in neocortical development and provide insight into the mechanisms by which its disruption leads to a plethora of structural abnormalities.
View details for DOI 10.1038/srep43708
View details for Web of Science ID 000395685000001
View details for PubMedID 28272472
View details for PubMedCentralID PMC5341122
Outcomes After Endoscopic Endonasal Resection of Craniopharyngiomas in the Pediatric Population.
2017; 108: 6–14
Craniopharyngiomas have traditionally been treated via open transcranial approaches. More recently, endoscopic transsphenoidal approaches have been increasingly used; however, few case series exist in the pediatric population.A retrospective review of patients (aged <18 years) undergoing endoscopic transsphenoidal resection of craniopharyngiomas between 1995 and 2016 was performed. Preoperative data included presenting symptoms, tumor size, location, and components. Postoperative outcomes included symptom resolution, visual outcomes, endocrine outcomes, disease recurrence, and major complications.Sixteen pediatric patients with mean age of 11.0 years (range, 5-15 years) were included. The median follow-up time was 56.2 months. Mean maximal tumor diameter was 3.98 cm. Most of the tumors had suprasellar (93.8%) and intrasellar (68.8%) components. The gross total resection rate was 93.8%. The most common presenting symptoms were vision changes (81.3%) and increased intracranial pressure (56.3%). Most patients (66.7%) had their presenting symptoms resolved by their first postoperative visit. Vision improved or remained normal in 69.2% of patients. Postoperatively, new incidence of panhypopituitarism or diabetes insipidus developed in 63.6% and 46.7% of patients, respectively. New hypothalamic obesity developed in 28.6% of patients. The postoperative cerebrospinal fluid leak rate was 18.8%. One patient died of intraventricular hemorrhage postoperatively. The major complication rate was 12.5%. Disease recurrence occurred in 1 patient with gross total resection (6.3%).Endoscopic transsphenoidal resection for craniopharyngiomas can achieve high rates of total resection with low rates of disease recurrence in larger tumors than previously described. However, hypothalamic-pituitary dysfunction and cerebrospinal fluid leak remain significant postoperative morbidities.
View details for PubMedID 28838874
A patient with a novel homozygous missense mutation in FTO and concomitant nonsense mutation in CETP
JOURNAL OF HUMAN GENETICS
2016; 61 (5): 395-403
The fat mass and obesity associated (FTO) gene has previously been associated with a variety of diseases and conditions, notably obesity, acute coronary syndrome and metabolic syndrome. Reports describing mutations in FTO as well as in FTO animal models have further demonstrated a role for FTO in the development of the brain and other organs. Here, we describe a patient born of consanguineous union who presented with microcephaly, developmental delay, behavioral abnormalities, dysmorphic facial features, hypotonia and other various phenotypic abnormalities. Whole-exome sequencing revealed a novel homozygous missense mutation in FTO and a nonsense mutation in the cholesteryl ester transfer protein (CETP). Exome copy number variation analysis revealed no disease-causing large duplications or deletions within coding regions. Patient's, her parents' and non-related control' fibroblasts were analyzed for morphologic defects, abnormal proliferation, apoptosis and transcriptome profile. We have shown that FTO is located in the nucleus of cells from each tested sample. Western blot analysis demonstrated no changes in patient FTO. Quantitative (qPCR) analysis revealed slightly decreased levels of FTO expression in patient cells compared with controls. No morphological or proliferation differences between the patient and control fibroblasts were observed. There is still much to be learned about the molecular mechanisms by which mutations in FTO contribute to such severe phenotypes.
View details for DOI 10.1038/jhg.2015.160
View details for Web of Science ID 000376504100005
View details for PubMedID 26740239
View details for PubMedCentralID PMC4880488
A rare case of congenital fibrosis of extraocular muscle type 1A due to KIF21A mutation with Marcus Gunn jaw-winking phenomenon.
European journal of paediatric neurology
2015; 19 (6): 743-746
Congenital fibrosis of the extraocular muscles (CFEOM1) is classically a congenital, non-progressive, restrictive strabismus syndrome characterized by bilateral ptosis and ophthalmoplegia with an infraducted position of the globes. This autosomal dominant syndrome is caused by mutations in the KIF21A gene.In this report we describe a 5-year-old boy, and his mother, both of whom have a mutation in the KIF21A gene, who possesses typical features of CFEOM1 syndrome. Besides displaying typical features of CFEOM1, he demonstrated Marcus Gunn jaw-winking phenomenon. The patient additionally had a positive family history of such features.This is first report of the coexistence of CFEOM and Marcus Gunn jaw-winking phenomenon in a patient with a KIF21A mutation from Turkey. We explain the phenotypic findings associated with mutations in KIF21A including CFEOM1A and Marcus Gunn jaw-winking phenomenon.
View details for DOI 10.1016/j.ejpn.2015.06.003
View details for PubMedID 26190014
Multimodal evaluation of CSF dynamics following extradural decompression for Chiari malformation Type I
JOURNAL OF NEUROSURGERY-SPINE
2015; 22 (6): 622-630
OBJECT Extradural decompression is a minimally invasive technique for treating Chiari malformation Type I (CM-I) that avoids the complications of dural opening. While there is no agreement on which surgical method is optimal, mounting evidence demonstrates that extradural decompression effectively treats clinical symptoms, with a minimal reoperation rate. Neurological symptoms such as headache may be related to obstructed flow of CSF, and one aspect of successful extradural decompression is improved CSF dynamics. In this series, the authors report on their use of phase-contrast cine flow MRI to assess CSF flow as well as satisfactory decompression. METHODS The authors describe their first surgical series of 18 patients with CM-I undergoing extradural decompression and correlate clinical improvement with radiological changes. Patients were categorized as having complete, partial, or no resolution of their symptoms. Posterior fossa area, cisterna magna area, and tonsillar herniation were assessed on T2-weighted MRI, whereas improvement of CSF flow was evaluated with phase-contrast cine flow MRI. All patients received standard pre- and postoperative MRI studies; 8 (44.4%) patients had pre- and postoperative phase-contrast cine, while the rest underwent cine studies only postoperatively. RESULTS All 18 patients presented with symptomatic CM-I, with imaging studies demonstrating tonsillar herniation ≥ 5 mm, and 2 patients had associated syringomelia. All patients underwent suboccipital decompression and C-1 laminectomy with splitting of the dura. Patients with complete resolution of their symptoms had a greater relative increase in cisterna magna area compared with those with only partial improvement (p = 0.022). In addition, in those with complete improvement the preoperative cisterna magna area was smaller than in those who had either partial (0.020) or no (0.025) improvement. Ten (91%) of the 11 patients with improved flow also had improvement in their symptoms. There was 1 postoperative complication of dysphagia and dysphonia. None of the patients have required a second operation. CONCLUSIONS Extradural decompression has the potential to be the first-line treatment for CM-I but has been lacking an objective measure by which to assess surgical success as well as the need for reoperation. An increase in the CSF spaces and improved CSF dynamics may be associated with resolution of clinical symptoms. Including cine imaging as part of routine pre- and postoperative evaluation can help identify which patients are most likely to benefit from surgery.
View details for DOI 10.3171/2014.10.SPINE1433
View details for Web of Science ID 000355031700010
View details for PubMedID 25746119
Management of Acute Traumatic Spinal Cord Injury
CURRENT TREATMENT OPTIONS IN NEUROLOGY
2015; 17 (2)
Spinal cord injury (SCI) causes significant morbidity and mortality. Clinical management in the acute setting needs to occur in the intensive care unit in order to identify, prevent, and treat secondary insults from local ischemia, hypotension, hypoxia, and inflammation. Maintenance of adequate perfusion and oxygenation is quintessential and a mean arterial pressure >85-90 mm Hg should be kept for at least 1 week. A cervical collar and full spinal precautions (log-roll, flat, holding C-spine) should be maintained until the spinal column has been fully evaluated by a spine surgeon. In patients with SCI, there is a high incidence of other bodily injuries, and there should be a low threshold to assess for visceral, pelvic, and long bone injuries. Computed tomography of the spine is superior to plain films, as the former rarely misses fractures, though caution needs to be exerted as occipitocervical dislocation can still be missed. To reliably assess the spinal neural elements, soft tissues, and ligamentous structures, magnetic resonance imaging is indicated and should be obtained within 48-72 h from the time of injury. All patients should be graded daily using the American Spinal Injury Association classification, with the first prognostic score at 72 h postinjury. Patients with high cervical cord (C4 or higher) injury should be intubated immediately, and those with lower cord injuries should be evaluated on a case-by-case basis. However, in the acute setting, respiratory mechanics will be disrupted with any spinal cord lesion above T11. Steroids have become extremely controversial, and the professional societies for neurosurgery in the United States have given a level 1 statement against their use in all patients. We, therefore, do not advocate for them at this time. With every SCI, a spine surgeon must be consulted to discuss operative vs nonoperative management strategies. Indications for surgery include a partial or progressive neurologic deficit, instability of the spine not allowing for mobilization, correction of a deformity, and prevention of potential neurologic compromise. Measures to prevent pulmonary emboli from deep venous thromboembolisms are necessary: IVC filters are recommended in bedbound patients and low-molecular weight heparins are superior to unfractionated heparin. Robust prevention of pressure ulcers as well as nutritional support should be a mainstay of treatment. Lastly, it is important to note that neurologic recovery is a several-year process. The most recovery occurs in the first year following injury, and therefore aggressive rehabilitation is crucial.
View details for DOI 10.1007/s11940-014-0334-1
View details for Web of Science ID 000351159000005
View details for PubMedID 25630995
Oversized self-expanding stents as an alternative to flow-diverters for blister-like aneurysms
2014; 36 (4): 351-355
Blister-like aneurysms (BLAs) are challenging to treat. Their friable nature makes them high risk for both traditional microsurgical and endovascular treatments. We discuss employing a single oversized self-expanding stent in the treatment of these treacherous lesions.A retrospective review from our institution was conducted. Five patients with BLAs were identified, who went on to be treated with a single oversized self-expanding stent, defined as 1 mm larger than the parent vessel, by the senior author (KRB), who is dual fellowship trained in both cerebrovascular/skull base microsurgery and endovascular neurosurgery. Additionally, a literature review was performed on BLAs treated with sole stenting and outcomes discussed.Our five patients had complete aneurysm occlusion at long-term follow-up and all had good neurological outcomes. The literature review demonstrated that most aneurysms at long-term follow-up were either completed occluded or progressively becoming occluded, with patients overall having a good functional outcome based on the modified Rankin scale (mRS).In our experience, oversized self-expanding stents are a treatment option that should be considered for BLAs. This strategy avoids the need for dual antiplatelet therapy and therefore increases its utility in the case of subarachnoid hemorrhage (SAH).
View details for DOI 10.1179/1743132814Y.0000000321
View details for Web of Science ID 000337109000008
View details for PubMedID 24617936
Thoracic epidural teratoma: case report and review of the literature.
Clinical medicine insights. Pathology
2014; 7: 15-20
Spinal teratomas comprise a rare subset of spinal cord tumors, and here, we describe an even rarer childhood thoracic extradural-intracanalicular teratoma. The clinical presentation, management, and pathophysiology of these tumors are reviewed to promote recognition and guide treatment of these lesions.We report the case of a 21-month-old boy who presented with marked spasticity, as well as failure to ambulate and meet motor milestones. Additionally, we provide a literature review of spinal teratomas, including their clinical presentation, work-up, pathophysiology, and underlying genetics.An MRI of the spine revealed a large dorsal epidural tumor extending from T3 to T10 with heterogeneous contrast enhancement and severe spinal cord compression. The tumor was resected revealing a cystic mass with tissue resembling hair, muscle, as well as cartilage; pathology confirmed the diagnosis of teratoma. Gross total resection was achieved, and the child eventually gained ambulatory function.Given that spinal teratomas are rare entities that can present with significant neurologic compromise, they must remain on clinicians' differentials. Unfortunately, the exact origin of these tumors remains inconclusive and requires further investigation.
View details for DOI 10.4137/CPath.S14723
View details for PubMedID 24940089
View details for PubMedCentralID PMC4055415
Hypoxia-inducible factor 1a is a Tsc1-regulated survival factor in newborn neurons in tuberous sclerosis complex
HUMAN MOLECULAR GENETICS
2013; 22 (9): 1725-1734
Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in TSC1 or TSC2 resulting in hyperactivity of the mammalian target of rapamycin and disabling brain lesions. These lesions contain misplaced neurons enriched in hypoxia-inducible factor 1a (HIF1a). However, the relationship between TSC1/2 and HIF1a and the function of HIF1a in TSC neurons remain unexplored. Here, we examine the degree of HIF1a activity and its function in newborn Tsc1(null) neurons in a mouse model of TSC. Using single cell electroporation in the neurogenic subventricular zone (SVZ) of neonatal mice, we deleted Tsc1 and generated olfactory lesions containing misplaced Tsc1(null) neurons as previously reported. These newborn neurons displayed elevated HIF1a-mediated transcriptional activity when compared with Tsc1 heterozygote neurons and a marked resistance to cell death induced by a HIF1a antagonist. Electroporation of Hif1a targeting short hairpin RNA (shRNA) or dominant negative HIF1a constructs resulted in 80-90% loss of Tsc1(null) newborn neurons although sparing SVZ stem cells. Consistent with this later finding, induction of Hif1a shRNA expression during synaptic integration thus bypassing neuron production also resulted in newborn neuron death. Collectively, these results suggest that HIF1a acts as a molecular determinant of newborn neuron survival and that its TSC1-dependent up-regulation gave Tsc1(null) neurons a survival advantage, despite their misplacement in a novel microenvironment.
View details for DOI 10.1093/hmg/ddt018
View details for Web of Science ID 000317431100003
View details for PubMedID 23349360
View details for PubMedCentralID PMC3613161
The relation between age and androgen deprivation therapy use among men in the Medicare population receiving radiation therapy for prostate cancer.
Journal of geriatric oncology
2013; 4 (1): 9–18
Neoadjuvant and concurrent androgen deprivation therapy (ncADT) is recommended for men with high-risk prostate cancer, but not low-risk cancer or short life expectancy. It is unclear whether the use of ncADT among older men in the community setting is aligned with the potential for clinical benefit.We used the Surveillance, Epidemiology, and End Results–Medicare database to assess patterns of ncADT use among men diagnosed with prostate cancer during 2004–2007 who received radiation therapy. Men were stratified according to tumor risk groups and life expectancy. We used logistic regression to identify factors associated with ncADT use within each risk group.There were 10,686 men in the sample (mean age 74.2 years; 83.4% white). The use of ncADT was 80.7%, 54.1%, and 27.8% in the high-, intermediate-, and low-risk groups, respectively. Men with a life expectancy<5 years had higher rates of ncADT use than men with a life expectancy≥10 years in all risk groups. Within each risk group, advancing age was associated with higher likelihood of receiving ncADT (odds ratio for men aged 80–84 compared to 67–69=1.93 (95% CI 1.37–2.70); 1.51 (95% CI 1.22–1.87); and 1.71 (95% CI 1.14–2.57) for high-, intermediate-, and low-risk groups, respectively).ncADT use is not consistent with guideline recommendations and is more frequent among men who are older, have shorter life expectancy, and are less likely to benefit from therapy.
View details for DOI 10.1016/j.jgo.2012.08.007
View details for PubMedID 23482846
View details for PubMedCentralID PMC3591488
Postnatal neurogenesis generates heterotopias, olfactory micronodules and cortical infiltration following single-cell Tsc1 deletion
HUMAN MOLECULAR GENETICS
2012; 21 (4): 799-810
Neurological symptoms in tuberous sclerosis complex (TSC) and associated brain lesions are thought to arise from abnormal embryonic neurogenesis due to inherited mutations in Tsc1 or Tsc2. Neurogenesis persists postnatally in the human subventricular zone (SVZ) where slow-growing tumors containing Tsc-mutant cells are generated in TSC patients. However, whether Tsc-mutant neurons from the postnatal SVZ contribute to brain lesions and abnormal circuit remodeling in forebrain structures remain unexplored. Here, we report the formation of olfactory lesions following conditional genetic Tsc1 deletion in the postnatal SVZ using transgenic mice or targeted single-cell electroporation. These lesions include migratory heterotopias and olfactory micronodules containing neurons with a hypertrophic dendritic tree. Most significantly, our data identify migrating glial and neuronal precursors that are re-routed and infiltrate forebrain structures (e.g. cortex) and become glia and neurons. These data show that Tsc1-mutant cells from the neonatal and juvenile SVZ generate brain lesions and structural abnormalities, which would not be visible using conventional non-invasive imaging. These findings also raise the hypothesis that micronodules and the persistent infiltration of cells to forebrain structures may contribute to network malfunction leading to progressive neuropsychiatric symptoms in TSC.
View details for DOI 10.1093/hmg/ddr511
View details for Web of Science ID 000299792800007
View details for PubMedID 22068588
View details for PubMedCentralID PMC3263992