Bio

Clinical Focus


  • Pediatric Neurosurgery
  • Brain and spinal cord tumors
  • Craniosynostosis
  • Congenital spinal conditions
  • Chiari malformation
  • Moya-moya disease
  • Spasticity
  • Myelomeningocele
  • Neuro-endoscopy

Academic Appointments


Professional Education


  • Medical Education: Stanford University School of Medicine (2012) CA
  • Fellowship: Seattle Children's Hospital Neurosurgery Fellowship (2020) WA
  • Residency: Stanford University Neurosurgery Residency (2019) CA

Publications

All Publications


  • Resection of hip heterotrophic ossification leads to resolution of autonomic nervous system dysfunction in a patient with spinal Charcot arthropathy: a case report. Spinal cord series and cases Fatemi, P., Prolo, L. M., Giori, N. J., Tharin, S. 2020; 6 (1): 41

    Abstract

    INTRODUCTION: Patients with complete spinal cord injury (SCI) may develop concurrent sequalae that interact and share symptoms; thus, a careful approach to diagnosis and management of new symptoms is crucial.CASE PRESENTATION: A patient with prior T4 complete SCI presented with progressive autonomic nervous system (ANS) dysfunction. The initial differential diagnosis included syringomyelia and lumbar Charcot arthropathy. He had comorbid heterotopic ossification (HO) of the left hip. Surprisingly, his autonomic symptoms resolved following resection of the HO. In hindsight, loss of motion through the hip caused by HO may have led to hinging through a previously asymptomatic lumbar Charcot joint, causing dysautonomia.DISCUSSION: ANS dysfunction is a disabling sequela of complete SCI and has a broad differential diagnosis. Hip immobility may be an indirect and overlooked cause due to the mechanical relationship between the hip and the lumbar spine.

    View details for DOI 10.1038/s41394-020-0286-5

    View details for PubMedID 32404876

  • Evaluating Shunt Survival Following Ventriculoperitoneal Shunting with and without Stereotactic Navigation in Previously Shunt-Naïve Patients. World neurosurgery Jin, M. C., Wu, A., Azad, T. D., Feng, A., Prolo, L. M., Veeravagu, A., Grant, G. A., Ratliff, J., Li, G. 2020

    View details for DOI 10.1016/j.wneu.2020.01.138

    View details for PubMedID 31996335

  • Recurrence of cavernous malformations after surgery in childhood. Journal of neurosurgery. Pediatrics Prolo, L. M., Jin, M. C., Loven, T., Vogel, H., Edwards, M. S., Steinberg, G. K., Grant, G. A. 2020: 1–10

    Abstract

    Cavernous malformations (CMs) are commonly treated cerebrovascular anomalies in the pediatric population; however, the data on radiographic recurrence of pediatric CMs after surgery are limited. The authors aimed to study the clinical presentation, outcomes, and recurrence rate following surgery for a large cohort of CMs in children.Pediatric patients (≤ 18 years old) who had a CM resected at a single institution were identified and retrospectively reviewed. Fisher's exact test of independence was used to assess differences in categorical variables. Survival curves were evaluated using the Mantel-Cox method.Fifty-three patients aged 3 months to 18 years underwent resection of 74 symptomatic CMs between 1996 and 2018 at a single institution. The median length of follow-up was 5.65 years. Patients most commonly presented with seizures (45.3%, n = 24) and the majority of CMs were cortical (58.0%, n = 43). Acute radiographic hemorrhage was common at presentation (64.2%, n = 34). Forty-two percent (n = 22) of patients presented with multiple CMs, and they were more likely to develop de novo lesions (71%) compared to patients presenting with a single CM (3.4%). Both radiographic hemorrhage and multiple CMs were independently prognostic for a higher risk of the patient requiring subsequent surgery. Fifty percent (n = 6) of the 12 patients with both risk factors required additional surgery within 2.5 years of initial surgery compared to none of the patients with neither risk factor (n = 9).Patients with either acute radiographic hemorrhage or multiple CMs are at higher risk for subsequent surgery and require long-term MRI surveillance. In contrast, patients with a single CM are unlikely to require additional surgery and may require less frequent routine imaging.

    View details for DOI 10.3171/2020.2.PEDS19543

    View details for PubMedID 32357336

  • Patterns of Care and Age-Specific Impact of Extent of Resection and Adjuvant Radiotherapy in Pediatric Pineoblastoma. Neurosurgery Jin, M. C., Prolo, L. M., Wu, A., Azad, T. D., Shi, S., Rodrigues, A. J., Soltys, S. G., Pollom, E. L., Li, G., Hiniker, S. M., Grant, G. A. 2020

    Abstract

    Pediatric pineoblastomas are highly aggressive tumors that portend poor outcomes despite multimodal management. Controversy remains regarding optimal disease management.To evaluate patterns of care and optimal clinical management of pediatric pineoblastoma.A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients diagnosed between 2004 and 2015 were queried from the National Cancer Database. Wilcoxon rank-sum statistics and chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate prognostic impact of covariates. Propensity-score matching was used to balance baseline characteristics.Older patients (age ≥ 4 yr) experienced improved overall survival compared to younger patients (age < 4 yr) (hazard ratio [HR] = 0.41; 95% CI 0.25-0.66). Older patients (adjusted odds ratio [aOR] = 5.21; 95% CI 2.61-10.78) and those residing in high-income regions (aOR = 3.16; 95% CI 1.21-8.61) received radiotherapy more frequently. Radiotherapy was independently associated with improved survival in older (adjusted HR [aHR] = 0.31; 95% CI 0.12-0.87) but not younger (aHR = 0.64; 95% CI 0.20-1.90) patients. The benefits of radiotherapy were more pronounced in patients receiving surgery than in those not receiving surgery (aHR [surgical patients] = 0.23; 95% CI 0.08-0.65; aHR [nonsurgical patients] = 0.46; 95% CI 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P = .041); extent of resection was not associated with survival in younger patients (P = .880).Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma.

    View details for DOI 10.1093/neuros/nyaa023

    View details for PubMedID 32110805

  • Deep Brain Stimulation for Pediatric Neuropsychiatric Disorders NEUROTECHNOLOGY AND BRAIN STIMULATION IN PEDIATRIC PSYCHIATRIC AND NEURODEVELOPMENTAL DISORDERS Quon, J. L., Kim, L. H., Quon, C. A., Prolo, L. M., Grant, G. A., Halpern, C. H., Oberman, L. M., Enticott, P. G. 2019: 237–52
  • Targeted genomic CRISPR-Cas9 screen identifies MAP4K4 as essential for glioblastoma invasion. Scientific reports Prolo, L. M., Li, A., Owen, S. F., Parker, J. J., Foshay, K., Nitta, R. T., Morgens, D. W., Bolin, S., Wilson, C. M., Vega L, J. C., Luo, E. J., Nwagbo, G., Waziri, A., Li, G., Reimer, R. J., Bassik, M. C., Grant, G. A. 2019; 9 (1): 14020

    Abstract

    Among high-grade brain tumors, glioblastoma is particularly difficult to treat, in part due to its highly infiltrative nature which contributes to the malignant phenotype and high mortality in patients. In order to better understand the signaling pathways underlying glioblastoma invasion, we performed the first large-scale CRISPR-Cas9 loss of function screen specifically designed to identify genes that facilitate cell invasion. We tested 4,574 genes predicted to be involved in trafficking and motility. Using a transwell invasion assay, we discovered 33 genes essential for invasion. Of the 11 genes we selected for secondary testing using a wound healing assay, 6 demonstrated a significant decrease in migration. The strongest regulator of invasion was mitogen-activated protein kinase 4 (MAP4K4). Targeting of MAP4K4 with single guide RNAs or a MAP4K4 inhibitor reduced migration and invasion in vitro. This effect was consistent across three additional patient derived glioblastoma cell lines. Analysis of epithelial-mesenchymal transition markers in U138 cells with lack or inhibition of MAP4K4 demonstrated protein expression consistent with a non-invasive state. Importantly, MAP4K4 inhibition limited migration in a subset of human glioma organotypic slice cultures. Our results identify MAP4K4 as a novel potential therapeutic target to limit glioblastoma invasion.

    View details for DOI 10.1038/s41598-019-50160-w

    View details for PubMedID 31570734

  • Uninstrumented Posterior Lumbar Interbody Fusion: Have Technological Advances in Stabilizing the Lumbar Spine Truly Improved Outcomes? WORLD NEUROSURGERY Prolo, L. M., Oklund, S. A., Zawadzki, N., Desai, M., Prolo, D. J. 2018; 115: 490–502
  • Uninstrumented Posterior Lumbar Interbody Fusion: Have Technological Advances in Stabilizing the Lumbar Spine Truly Improved Outcomes? World neurosurgery Prolo, L. M., Oklund, S. A., Zawadzki, N., Desai, M., Prolo, D. J. 2018

    Abstract

    BACKGROUND: Since the 1980s, numerous operations have replaced posterior lumbar interbody fusion (PLIF) with human bone. These operations often involve expensive implants and complex procedures. Escalating expenditures in lumbar fusion surgery warrant re-evaluation of classical PLIF with allogeneic ilium and without instrumentation. The purpose of this study was to determine the long-term fusion rate and clinical outcomes of PLIF with allogeneic bone (allo-PLIF).METHODS: Between 1981 and 2006, 321 patients aged 12-80 years underwent 339 1-level or 2-level allo-PLIFs for degenerative instability and were followed for 1-28 years. Fusion status was determined by radiographs and as available, by computed tomography scans. Clinical outcome was assessed by the Economic/Functional Outcome Scale.RESULTS: Of the 321 patients, 308 were followed postoperatively (average 6.7 years) and 297 (96%) fused. Fusion rates were lower for patients with substance abuse (89%, P= 0.007). Clinical outcomes in 87% of patients were excellent (52%) or good (35%). Economic/Functional Outcome Scale scores after initial allo-PLIF on average increased 5.2 points. Successful fusion correlated with nearly a 2-point gain in outcome score (P= 0.001). A positive association between a patient characteristic and outcome was observed only with age 65 years and greater, whereas negative associations in clinical outcomes were observed with mental illness, substance abuse, heavy stress to the low back, or industrial injuries. The total complication rate was7%.CONCLUSIONS: With 3 decades of follow-up, we found that successful clinical outcomes are highly correlated with solid fusion using only allogeneic iliac bone.

    View details for PubMedID 29631080

  • Occipital Dermal Sinus Tract JOURNAL OF PEDIATRICS Prolo, L. M., Grant, G. A. 2018; 193: 276

    View details for PubMedID 29174077

  • Anterolateral approach to the upper cervical spine: Case report and operative technique HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK Song, Y., Tharin, S., Divi, V., Prolo, L. M., Sirjani, D. B. 2015; 37 (9): E115-E119

    Abstract

    Transcervical approaches to the upper cervical spine are challenging because several upper anterior neurovascular structures need to be displaced to provide access. Although various techniques have been described, the anterolateral approach is one of the safest and most effective methods available to access the anterior C2-C3 disc space. Despite the approach's efficacy, however, it can cause postoperative complications because of, at least partly, the inter-surgeon differences in the methods by which the larynx and hypopharynx are displaced medially.We present a case report of a patient treated with a modified anterolateral approach to C2-C3. The approach provided excellent visualization while protecting vital structures. The patient recovered without any postoperative dysphagia or other surgical complications.The anterolateral approach to C2-C3 described herein safely protects the contents of the submandibular triangle while providing a wide exposure for direct access to the C2-C3 disc space. © 2015 Wiley Periodicals, Inc. Head Neck 37: E115-E119, 2015.

    View details for DOI 10.1002/hed.23951

    View details for Web of Science ID 000359605700004

    View details for PubMedID 25522016

  • Anterolateral approach to the upper cervical spine: Case report and operative technique. Head & neck Song, Y., Tharin, S., Divi, V., Prolo, L. M., Sirjani, D. B. 2015; 37 (9): E115-9

    Abstract

    Transcervical approaches to the upper cervical spine are challenging because several upper anterior neurovascular structures need to be displaced to provide access. Although various techniques have been described, the anterolateral approach is one of the safest and most effective methods available to access the anterior C2-C3 disc space. Despite the approach's efficacy, however, it can cause postoperative complications because of, at least partly, the inter-surgeon differences in the methods by which the larynx and hypopharynx are displaced medially.We present a case report of a patient treated with a modified anterolateral approach to C2-C3. The approach provided excellent visualization while protecting vital structures. The patient recovered without any postoperative dysphagia or other surgical complications.The anterolateral approach to C2-C3 described herein safely protects the contents of the submandibular triangle while providing a wide exposure for direct access to the C2-C3 disc space. © 2015 Wiley Periodicals, Inc. Head Neck 37: E115-E119, 2015.

    View details for DOI 10.1002/hed.23951

    View details for PubMedID 25522016

  • Vesicular uptake and exocytosis of L-aspartate is independent of sialin FASEB JOURNAL Morland, C., Nordengen, K., Larsson, M., Prolo, L. M., Farzampour, Z., Reimer, R. J., Gundersen, V. 2013; 27 (3): 1264-1274

    Abstract

    The mechanism of release and the role of l-aspartate as a central neurotransmitter are controversial. A vesicular release mechanism for l-aspartate has been difficult to prove, as no vesicular l-aspartate transporter was identified until it was found that sialin could transport l-aspartate and l-glutamate when reconstituted into liposomes. We sought to clarify the release mechanism of l-aspartate and the role of sialin in this process by combining l-aspartate uptake studies in isolated synaptic vesicles with immunocyotchemical investigations of hippocampal slices. We found that radiolabeled l-aspartate was taken up into synaptic vesicles. The vesicular l-aspartate uptake, relative to the l-glutamate uptake, was twice as high in the hippocampus as in the whole brain, the striatum, and the entorhinal and frontal cortices and was not inhibited by l-glutamate. We further show that sialin is not essential for exocytosis of l-aspartate, as there was no difference in ATP-dependent l-aspartate uptake in synaptic vesicles from sialin-knockout and wild-type mice. In addition, expression of sialin in PC12 cells did not result in significant vesicle uptake of l-aspartate, and depolarization-induced depletion of l-aspartate from hippocampal nerve terminals was similar in hippocampal slices from sialin-knockout and wild-type mice. Further, there was no evidence for nonvesicular release of l-aspartate via volume-regulated anion channels or plasma membrane excitatory amino acid transporters. This suggests that l-aspartate is exocytotically released from nerve terminals after vesicular accumulation by a transporter other than sialin.

    View details for DOI 10.1096/fj.12-206300

    View details for Web of Science ID 000315585200038

    View details for PubMedID 23221336

    View details for PubMedCentralID PMC3574276

  • The Lysosomal Sialic Acid Transporter Sialin Is Required for Normal CNS Myelination JOURNAL OF NEUROSCIENCE Prolo, L. M., Vogel, H., Reimer, R. J. 2009; 29 (49): 15355-15365

    Abstract

    Salla disease and infantile sialic acid storage disease are autosomal recessive lysosomal storage disorders caused by mutations in the gene encoding sialin, a membrane protein that transports free sialic acid out of the lysosome after it is cleaved from sialoglycoconjugates undergoing degradation. Accumulation of sialic acid in lysosomes defines these disorders, and the clinical phenotype is characterized by neurodevelopmental defects, including severe CNS hypomyelination. In this study, we used a sialin-deficient mouse to address how loss of sialin leads to the defect in myelination. Behavioral analysis of the sialin(-/-) mouse demonstrates poor coordination, seizures, and premature death. Analysis by histology, electron microscopy, and Western blotting reveals a decrease in myelination of the CNS but normal neuronal cytoarchitecture and normal myelination of the PNS. To investigate potential mechanisms underlying CNS hypomyelination, we studied myelination and oligodendrocyte development in optic nerves. We found reduced numbers of myelinated axons in optic nerves from sialin(-/-) mice, but the myelin that was present appeared grossly normal. Migration and density of oligodendrocyte precursor cells were normal; however, a marked decrease in the number of postmitotic oligodendrocytes and an associated increase in the number of apoptotic cells during the later stages of myelinogenesis were observed. These findings suggest that a defect in maturation of cells in the oligodendrocyte lineage leads to increased apoptosis and underlies the myelination defect associated with sialin loss.

    View details for DOI 10.1523/JNEUROSCI.3005-09.2009

    View details for PubMedID 20007460

  • Physiology - Keeping it regular with protons NATURE Prolo, L. M., Goodman, M. B. 2008; 452 (7183): 35-36

    View details for DOI 10.1038/452035a

    View details for Web of Science ID 000253671900033

    View details for PubMedID 18322516

  • Circadian rhythm generation and entrainment in astrocytes JOURNAL OF NEUROSCIENCE Prolo, L. M., Takahashi, J. S., Herzog, E. D. 2005; 25 (2): 404-408

    Abstract

    In mammals, the master circadian pacemaker is considered the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN consists of a heterogeneous population of neurons and relatively understudied glia. We investigated whether glia, like neurons, rhythmically express circadian genes. We generated pure cultures of cortical astrocytes from Period2::luciferase (Per2::luc) knock-in mice and Period1::luciferase (Per1::luc) transgenic rats and recorded bioluminescence as a real-time reporter of gene activity. We found that rat Per1::luc and mouse Per2::luc astroglia express circadian rhythms with a genetically determined period. These rhythms damped out after several days but were reinitiated by a variety of treatments, including a full volume exchange of the medium. If cultures were treated before damping out, the phase of Per1::luc rhythmicity was shifted, depending on the time of the pulse relative to the peak of Per1 expression. Glial rhythms entrained to daily 1.5 degrees C temperature cycles and were significantly sustained when cocultured with explants of the adult SCN but not with cortical explants. Thus, multiple signals, including a diffusible factor(s) from the SCN, are sufficient to either entrain or restart circadian oscillations in cortical glia.

    View details for DOI 10.1523/JNEUROSCI.4133-04.2005

    View details for Web of Science ID 000226271400014

    View details for PubMedID 15647483

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