Browsing by Author "Ordaz, Josue D."
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Item Delayed presentation of a traumatic scalp arteriovenous fistula(Scientific Scholar, 2021-05-25) Ordaz, Josue D.; Villelli, Nicolas W.; Bohsntedt, Bradley N.; Ackerman, Laurie L.; Neurological Surgery, School of MedicineBackground: Arteriovenous (AV) fistulas of the scalp are extracranial vascular malformations commonly caused by trauma and typically present within 3 years. Although they follow a benign course, they can be esthetically displeasing. Case description: We present an atypical onset of scalp AV fistula in a patient with a 1-year history of the left-sided pulsatile tinnitus and scalp swelling 7 years after a traumatic epidural hematoma evacuation. Our patient was found to have an 8 mm AV fistula supplied by the deep temporal artery. Endovascular embolization was performed using eight coils. There was no complication from the procedure, and the patient's pulsatile tinnitus and swelling resolved immediately after embolization. Follow-up angiogram demonstrated complete obliteration of the AV fistula. Conclusion: Delayed presentation of traumatic scalp AV fistula is very rare, and it is important to keep this in the differential in patients with scalp swelling after head trauma.Item Descending motor circuitry required for NT-3 mediated locomotor recovery after spinal cord injury in mice(Nature Research, 2019-12-20) Han, Qi; Ordaz, Josue D.; Liu, Nai-Kui; Richardson, Zoe; Wu, Wei; Xia, Yongzhi; Qu, Wenrui; Wang, Ying; Dai, Heqiao; Zhang, Yi Ping; Shields, Christopher B.; Smith, George M.; Xu, Xiao-Ming; Neurological Surgery, School of MedicineLocomotor function, mediated by lumbar neural circuitry, is modulated by descending spinal pathways. Spinal cord injury (SCI) interrupts descending projections and denervates lumbar motor neurons (MNs). We previously reported that retrogradely transported neurotrophin-3 (NT-3) to lumbar MNs attenuated SCI-induced lumbar MN dendritic atrophy and enabled functional recovery after a rostral thoracic contusion. Here we functionally dissected the role of descending neural pathways in response to NT-3-mediated recovery after a T9 contusive SCI in mice. We find that residual projections to lumbar MNs are required to produce leg movements after SCI. Next, we show that the spared descending propriospinal pathway, rather than other pathways (including the corticospinal, rubrospinal, serotonergic, and dopaminergic pathways), accounts for NT-3-enhanced recovery. Lastly, we show that NT-3 induced propriospino-MN circuit reorganization after the T9 contusion via promotion of dendritic regrowth rather than prevention of dendritic atrophy.Item Establishment and characterization of patient-derived xenograft of a rare pediatric anaplastic pleomorphic xanthoastrocytoma (PXA) bearing a CDC42SE2-BRAF fusion(Springer Nature, 2023-06-06) Damayanti, Nur P.; Saadatzadeh, M. Reza; Dobrota, Erika; Ordaz, Josue D.; Bailey, Barbara J.; Pandya, Pankita H.; Bijangi-Vishehsaraei, Khadijeh; Shannon, Harlan E.; Alfonso, Anthony; Coy, Kathy; Trowbridge, Melissa; Sinn, Anthony L.; Zhang, Zhong-Yin; Gallagher, Rosa I.; Wulfkuhle, Julia; Petricoin, Emanuel; Richardson, Angela M.; Marshall, Mark S.; Lion, Alex; Ferguson, Michael J.; Balsara, Karl E.; Pollok, Karen E.; Neurological Surgery, School of MedicinePleomorphic xanthoastrocytoma (PXA) is a rare subset of primary pediatric glioma with 70% 5-year disease free survival. However, up to 20% of cases present with local recurrence and malignant transformation into more aggressive type anaplastic PXA (AXPA) or glioblastoma. The understanding of disease etiology and mechanisms driving PXA and APXA are limited, and there is no standard of care. Therefore, development of relevant preclinical models to investigate molecular underpinnings of disease and to guide novel therapeutic approaches are of interest. Here, for the first time we established, and characterized a patient-derived xenograft (PDX) from a leptomeningeal spread of a patient with recurrent APXA bearing a novel CDC42SE2-BRAF fusion. An integrated -omics analysis was conducted to assess model fidelity of the genomic, transcriptomic, and proteomic/phosphoproteomic landscapes. A stable xenoline was derived directly from the patient recurrent tumor and maintained in 2D and 3D culture systems. Conserved histology features between the PDX and matched APXA specimen were maintained through serial passages. Whole exome sequencing (WES) demonstrated a high degree of conservation in the genomic landscape between PDX and matched human tumor, including small variants (Pearson's r = 0.794-0.839) and tumor mutational burden (~ 3 mutations/MB). Large chromosomal variations including chromosomal gains and losses were preserved in PDX. Notably, chromosomal gain in chromosomes 4-9, 17 and 18 and loss in the short arm of chromosome 9 associated with homozygous 9p21.3 deletion involving CDKN2A/B locus were identified in both patient tumor and PDX sample. Moreover, chromosomal rearrangement involving 7q34 fusion; CDC42SE-BRAF t (5;7) (q31.1, q34) (5:130,721,239, 7:140,482,820) was identified in the PDX tumor, xenoline and matched human tumor. Transcriptomic profile of the patient's tumor was retained in PDX (Pearson r = 0.88) and in xenoline (Pearson r = 0.63) as well as preservation of enriched signaling pathways (FDR Adjusted P < 0.05) including MAPK, EGFR and PI3K/AKT pathways. The multi-omics data of (WES, transcriptome, and reverse phase protein array (RPPA) was integrated to deduce potential actionable pathways for treatment (FDR < 0.05) including KEGG01521, KEGG05202, and KEGG05200. Both xenoline and PDX were resistant to the MEK inhibitors trametinib or mirdametinib at clinically relevant doses, recapitulating the patient's resistance to such treatment in the clinic. This set of APXA models will serve as a preclinical resource for developing novel therapeutic regimens for rare anaplastic PXAs and pediatric high-grade gliomas bearing BRAF fusions.Item Iatrogenic Spinal Deformity Following Spinal Intradural Arachnoid Cyst Fenestration Despite Minimal Access With Laminoplasty and Endoscopy in a Pediatric Patient(Cureus, 2022-02-09) Ordaz, Josue D.; Huh, Andrew; Desai, Virendra; Raskin, Jeffrey S.; Neurological Surgery, School of MedicineSpinal intradural arachnoid cysts (SAC) are non-neoplastic lesions that can cause spinal cord compression and present with myelopathy, radiculopathy, and/or back pain. Because these cysts typically span multiple levels, endoscopy could be a useful tool to avoid wide exposure. We present an 8-year-old patient with a history of gait imbalance and urinary incontinence who was found to have a SAC spanning C7 to T6 causing spinal cord compression. An osteoplastic laminoplasty was performed from T4 to T7 followed by ultrasonic verification of intracystic septations, dural opening, and cyst fenestration. A flexible endoscope was then introduced into the cystic cavity to guide complete rostral and caudal decompression of the arachnoid cyst. At six months follow-up, the patient was able to ambulate independently, but his urinary incontinence remained unchanged. Despite the combination of ultrasound and neuroendoscopy to minimize exposure, our patient suffered from worsening kyphosis from 36 degrees preoperative to 55 degrees postoperative and worsening scoliosis from 17 to 39 degrees which required treatment with a thoracolumbar sacral orthosis. Preoperative imaging demonstrated a reverse S-shaped scoliosis with the apex at T6 and T7 which were the levels included in the laminoplasty. This illustrates the need for careful preoperative risk stratification to avoid this postoperative complication.Item Intracranial Vasospasm After Evacuation of Acute Spontaneous Subdural Hematoma(Cureus, 2021-05-27) Witten, Andrew J.; Ordaz, Josue D.; Alentado, Vincent J.; Bohnstedt, Bradley; Neurological Surgery, School of MedicineCerebral vasospasm is a well-known entity following aneurysmal subarachnoid hemorrhage. While it has been described in trauma, it has been much less studied. There have been no previous reports of cerebral vasospasm following spontaneous subdural hematoma or after subdural hematoma evacuation. In this case report, we present a 38-year-old otherwise healthy female who suffered an acute spontaneous subdural hematoma. After surgical evacuation of her hematoma, she developed neurologic decline. Computer tomography angiography demonstrated intracranial vasospasm. She was treated with blood pressure augmentation and nimodipine. She went on to make a full neurologic recovery.To our knowledge, this is the first reported case of cerebral vasospasm after acute spontaneous subdural hematoma or after subdural hematoma evacuation, and the patient recovered without sequelae. The promising outcome of this case may provide a framework for future similar cases. Neurosurgeons and intensivists should keep cerebral vasospasm in their differentials for patients who have neurologic decline after craniotomy for acute subdural hematoma and have an otherwise negative scan for new acute abnormality.Item Optogenetics and its application in neural degeneration and regeneration(Wolters Kluwer, 2017-08) Ordaz, Josue D.; Wu, Wei; Xu, Xiao-Ming; Neurological Surgery, School of MedicineNeural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and temporal control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited. This short review presents representative work in optogenetics in disease models such as spinal cord injury, multiple sclerosis, epilepsy, Alzheimer’s disease and Parkinson’s disease. It is aimed to provide a broader perspective on optogenetic therapeutic potential in neurodegeneration and neural regeneration.Item Preoperative Embolization With Fused CT Angiography and Tractography Facilitates Safe Resection of a Spetzler-Martin Grade IV Arteriovenous Malformation(Cureus, 2021-12-24) Weyhenmeyer, Jonathan; Ordaz, Josue D.; Gadol, Aaron Cohen; Shah, Mitesh; Neurological Surgery, School of MedicineBrain arteriovenous malformations (BAVMs) are high-flow vascular lesions that have a propensity to rupture resulting in high rates of morbidity and mortality. Microsurgical resection of BAVMs is the standard of care for high-risk, resectable lesions. Multiple imaging modalities aid in the surgical planning and resection of high-grade BAVMs, but all have hidden variables that would prove useful if available. We present a 20-year-old male with a ruptured BAVM with concern for the involvement of the corticospinal tract (CST) and basal ganglia. We describe the melding of computed tomography angiography (CTA) and diffusion tensor imaging (DTI) in addition to preoperative embolization to aid in the planning and resection of a lesion close to eloquent structures. Post-operative CTA and DTI showed a total resection of the lesion with retained CST white matter tracts, and the patient retained the functional ability of the contralateral limbs. The combination of CTA, brain DTI, and preoperative embolization provides a framework to improve the safety of resection of BAVMs that occur near eloquent brain networks.Item Restoring cellular energetics promotes axon regeneration and functional recovery after spinal cord injury(Cell Press, 2020-03-03) Han, Qi; Xie, Yuxiang; Ordaz, Josue D.; Huh, Andrew J.; Huang, Ning; Wu, Wei; Liu, Naikui; Chamberlain, Kelly A.; Sheng, Zu-Hang; Xu, Xiao-Ming; Neurological Surgery, School of MedicineAxonal regeneration in the central nervous system (CNS) is a highly energy-demanding process. Extrinsic insults and intrinsic restrictions lead to an energy crisis in injured axons, raising the question of whether recovering energy deficits facilitates regeneration. Here, we reveal that enhancing axonal mitochondrial transport by deleting syntaphilin (Snph) recovers injury-induced mitochondrial depolarization. Using three CNS injury mouse models, we demonstrate that Snph-/- mice display enhanced corticospinal tract (CST) regeneration passing through a spinal cord lesion, accelerated regrowth of monoaminergic axons across a transection gap, and increased compensatory sprouting of uninjured CST. Notably, regenerated CST axons form functional synapses and promote motor functional recovery. Administration of the bioenergetic compound creatine boosts CST regenerative capacity in Snph-/- mice. Our study provides mechanistic insights into intrinsic regeneration failure in CNS and suggests that enhancing mitochondrial transport and cellular energetics are promising strategies to promote regeneration and functional restoration after CNS injuries.Item Single-Institution Comparative Study of MR-guided Laser Interstitial Thermal Therapy and Open Corpus Callosotomy(Elsevier, 2023-07) Ordaz, Josue D.; Vishnubhotla, Ramana; Alfonso, Anthony; Budnick, Hailey; Wen, Qiuting; Radhakrishnan, Rupa; Raskin, Jeffrey; Neurological Surgery, School of MedicineObjective Open corpus callosotomy (CC) poses a higher risk of perioperative morbidity than does magnetic resonance–guided laser interstitial thermal therapy (MRgLITT) for treatment of drop and generalized seizures without documented superiority. We present a single-institution comparison between open and MRgLITT CC. Methods A 2-year retrospective review was performed of patients who underwent open and MRgLITT CC (January 2019–January 2021). Demographics, surgical outcome data, hospital costs, and interhemispheric connectivity with diffusion tensor imaging were compared. Results The average age in years was 9.3 and 11.4 for CC (n = 4) and MRgLITT (n = 9), respectively. Preoperative drop seizure frequency was higher in CC (25 vs. 14.5 seizures/day; P = 0.59). At 10 months follow-up, the reduction in drop seizure frequency was better in open CC, but not statistically significant (93.8% vs. 64.3%; P = 0.21). The extent of CC ablation did not correlate with seizure reduction (Pearson coefficient = 0.09). An inverse correlation between interhemispheric connectivity change (diffusion tensor imaging analysis) and drop seizure frequency reduction was noted (Pearson coefficient = –0.97). Total hospital cost was significantly lower in MRgLITT ($67,754 vs. $107,111; P = 0.004), attributed to lower intensive care unit (1.1 vs. 4 days; P= 0.004) and total hospital stay (1.8 vs. 10.5 days; P = 0.0001). Postoperative hydrocephalus was present in 75% of patients in the CC group compared with zero in the MRgLITT group. Conclusions Our middle-volume single-institution experience shows the safety, efficacy, and cost-effective benefit of MRgLITT compared with the traditional CC with therapeutic equipoise. This study is limited by the number of patients and, hence, further patient enrollment or multicenter study is warranted.Item Targeting of a Photosensitizer to the Mitochondrion Enhances the Potency of Photodynamic Therapy(American Chemical Society, 2018-06-30) Mahalingam, Sakkarapalayam M.; Ordaz, Josue D.; Low, Philip S.; Medicine, School of MedicinePhotodynamic therapy (PDT) involves use of a photosensitizer, whose activation with light leads to the production of singlet oxygen (SOS), generation of reactive oxygen species (ROS), and initiation of associated cell toxicity. Because a cell's mitochondria constitute sites where oxygen levels are high, ROS can be readily produced, and apoptosis is commonly initiated. Therefore, an ideal PDT agent might be a potent photosensitizer that could naturally accumulate in mitochondria. Although a number of mitochondria-targeting moieties, including triphenylphosphine, guanidinium, and bisguanidium, have been identified, a quantitative comparison of their efficacies in targeting mitochondria has not been performed. In this study, we have prepared triphenylphosphine, guanidinium, and bisguanidium derivatives of the FDA-approved PDT agent verteporfin (Visudyne, benzoporphyrin derivative-monoacid ring A: BPD-MA) and compared their abilities to induce the intracellular perturbations common to potent PDT agents. Cellular parameters examined included subcellular localization of the verteporfin, real-time monitoring of SOS production, quantitation of reactive oxygen species (ROS) generation, analysis of mitochondria and chromatin integrity, characterization of cytoskeletal disruption and evaluation of cytochrome C release as a measure of apoptosis. An analysis of these parameters demonstrates that the triphenylphosphine derivative (0323) has better mitochondria-targeting efficacy, SOS production, and mitochondria membrane toxicity than either unmodified verteporfin or its guanidinium derivatives. Consistent with this potency, 0323 also induced the most prominent mitochondria swelling, actin depolymerization, pyknosis, and cytochrome C release. We conclude that triphenylphosphine has a better mitochondria-targeting moiety than guanidinium or bis-guanidinium and those PDT photosensitizers with improved cytotoxicities can be prepared by conjugating a mitochondria-targeting moiety to the desired photosensitizer.