Neurosurgery Commons^™

Potential Of Mesenchymal Stem Cells Alone, Or In Combination, To Treat Traumatic Brain Injury, Alison E. Willing, Mahasweta Das, Mark Howell, Shyam S. Mohapatra, Subhra Mohapatra

Neurosurgery and Brain Repair Faculty Publications

Traumatic brain injury (TBI) causes death and disability in the United States and around the world. The traumatic insult causes the mechanical injury of the brain and primary cellular death. While a comprehensive pathological mechanism of TBI is still lacking, the focus of the TBI research is concentrated on understanding the pathophysiology and developing suitable therapeutic approaches. Given the complexities in pathophysiology involving interconnected immunologic, inflammatory, and neurological cascades occurring after TBI, the therapies directed to a single mechanism fail in the clinical trials. This has led to the development of the paradigm of a combination therapeutic approach against TBI. …

Novel Titanium Cages For Minimally Invasive Lateral Lumbar Interbody Fusion: First Assessment Of Subsidence, Paul R. Krafft, Brooks Osburn, Andrew C. Vivas, Gautam Rao, Puya Alikhani

Neurosurgery and Brain Repair Faculty Publications

Introduction: Implant subsidence is a potential complication of spinal interbody fusion and may negatively affect patients subjected to procedures relying on indirect decompression such as minimally invasive transpsoas lateral lumbar interbody fusion (LLIF). The porous architecture of a recently developed titanium intervertebral cage maximizes bone-to-implant contact and minimizes stress shielding in laboratory experiments; however, its subsidence rate in patients has not yet been evaluated. The goal of this current study was to evaluate implant subsidence in patients subjected to LLIF.

Methods: Our institutional review board-approved single-center experience included 29 patients who underwent 30 minimally invasive LLIF from July 2017 to …

Mesenchymal Stem Cell Therapy Alleviates The Neuroinflammation Associated With Acquired Brain Injury, Brooke Bonsack, Sydney Corey, Alex Shear, Matt Heyck, Blaise Cozene, Nadia Sadanandan, Henry Zhang, Bella Gonzales-Portillo, Michael Sheyner, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Ischemic stroke and traumatic brain injury (TBI) comprise two particularly prevalent and costly examples of acquired brain injury (ABI). Following stroke or TBI, primary cell death and secondary cell death closely model disease progression and worsen outcomes. Mounting evidence indicates that long-term neuroinflammation extensively exacerbates the secondary deterioration of brain structure and function. Due to their immunomodulatory and regenerative properties, mesenchymal stem cell transplants have emerged as a promising approach to treating this facet of stroke and TBI pathology. In this review, we summarize the classification of cell death in ABI and discuss the prominent role of inflammation. We then …

Advancing Stem Cell Therapy For Repair Of Damaged Lung Microvasculature In Amyotrophic Lateral Sclerosis, Svitlana Garbuzova-Davis, Robert Shell, Hilmi Mustafa, Surafuale Hailu, Alison E. Willing, Paul R. Sanberg, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Amyotrophic lateral sclerosis (ALS) is a fatal disease of motor neuron degeneration in the brain and spinal cord. Progressive paralysis of the diaphragm and other respiratory muscles leading to respiratory dysfunction and failure is the most common cause of death in ALS patients. Respiratory impairment has also been shown in animal models of ALS. Vascular pathology is another recently recognized hallmark of ALS pathogenesis. Central nervous system (CNS) capillary damage is a shared disease element in ALS rodent models and ALS patients. Microvascular impairment outside of the CNS, such as in the lungs, may occur in ALS, triggering lung damage …

Foraminal Ligaments Tether Upper Cervical Nerve Roots: A Potential Cause Of Postoperative C5 Palsy, Andrew S. Jack, Brooks R. Osburn, Zane A. Tymchak, Wyatt L. Ramey, Rod J. Oskouian, Robert A. Hart, Jens R. Chapman, Line G. Jacques, R. Shane Tubbs

Neurosurgery and Brain Repair Faculty Publications

Background: Nerve root tethering upon dorsal spinal cord (SC) migration has been proposed as a potential mechanism for postoperative C5 palsy (C5P). To our knowledge, this is the first study to investigate this relationship by anatomically comparing C5–C6 nerve root translation before and after root untethering by cutting the cervical foraminal ligaments (FL).

Objective: The aim of this study is to determine if C5 root untethering through FL cutting results in increased root translation.

Methods: Six cadaveric dissections were performed. Nerve roots were exposed via C4–C6 corpectomies and supraclavicular brachial plexus exposure. Pins were inserted into the C5–C6 roots and …

Cell Therapy For Central Nervous System Disorders: Current Obstacles To Progress, Takao Yasuhara, Satoshi Kawauchi, Kyohei Kin, Jun Morimoto, Masahiro Kameda, Tatsuya Sasaki, Brooke Bonsack, Chase Kingsbury, Naoki Tajiri, Cesar V. Borlongan, Isao Date

Neurosurgery and Brain Repair Faculty Publications

Cell therapy for disorders of the central nervous system has progressed to a new level of clinical application. Various clinical studies are underway for Parkinson's disease, stroke, traumatic brain injury, and various other neurological diseases. Recent biotechnological developments in cell therapy have taken advantage of the technology of induced pluripotent stem (iPS) cells. The advent of iPS cells has provided a robust stem cell donor source for neurorestoration via transplantation. Additionally, iPS cells have served as a platform for the discovery of therapeutics drugs, allowing breakthroughs in our understanding of the pathology and treatment of neurological diseases. Despite these recent …

Translating Intracarotid Artery Transplantation Of Bone Marrow-Derived Ncs-01 Cells For Ischemic Stroke: Behavioral And Histological Readouts And Mechanistic Insights Into Stem Cell Therapy, Yuji Kaneko, Jea-Young Lee, Naoki Tajiri, Julian P. Tuazon, Trenton Lippert, Eleonora Russo, Seong-Jin Yu, Brooke Bonsack, Sydney Corey, Alexandreya B. Coats, Chase Kingsbury, Thomas N. Chase, Minako Koga, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

The present study used in vitro and in vivo stroke models to demonstrate the safety, efficacy, and mechanism of action of adult human bone marrow-derived NCS-01 cells. Coculture with NCS-01 cells protected primary rat cortical cells or human neural progenitor cells from oxygen glucose deprivation. Adult rats that were subjected to middle cerebral artery occlusion, transiently or permanently, and subsequently received intracarotid artery or intravenous transplants of NCS-01 cells displayed dose-dependent improvements in motor and neurological behaviors, and reductions in infarct area and peri-infarct cell loss, much better than intravenous administration. The optimal dose was 7.5 × 106 cells/mL when …

Early Acid/Base And Electrolyte Changes In Permanent Middle Cerebral Artery Occlusion: Aged Male And Female Rats, Sarah R. Martha, Lisa A. Collier, Stephanie M. Davis, Sarah J. Goodwin, David Powell, Doug Lukins, Justin F. Fraser, Keith R. Pennypacker

Neurosurgery Faculty Publications

BACKGROUND: Early changes in acid/base and electrolyte concentrations could provide insights into the development of neuropathology at the onset of stroke. We evaluated associations between acid/base and electrolyte concentrations, and outcomes in permanent middle cerebral artery occlusion (pMCAO) model.

METHODS: 18-month-old male and female Sprague-Dawley rats underwent pMCAO. Pre-, post- (7 min after occlusion), and at 72 hr of pMCAO venous blood samples provided pH, carbon dioxide, oxygen, glucose, hematocrit, hemoglobin, and electrolyte values of ionized calcium, potassium, and sodium. Multiple linear regression determined predictors of infarct and edema volumes from these values, Kaplan-Meier curve analyzed morality between males and …

The Effect Of Haptoglobin Phenotypes On Markers Of Neuroinflammation In Patients With Aneurysmal Subarachnoid Hemorrhage, Kevin Hatton

Theses and Dissertations--Clinical and Translational Science

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe form of hemorrhagic stroke resulting from the spontaneous rupture of an intracranial aneurysm and release of oxygenated blood into the subarachnoid space. In the United States alone, aSAH occurs in approximately 30,000 patients each year and occurs, primarily, in otherwise healthy adults, frequently without warning. Sadly, approximately 40% of patients with aSAH will die in the first 30 days. Of those who survive, only about 75% will be able to live semi-independently again and only about 60% will be able to return to work.

Delayed brain injuries (DBI), which may affect up to …

Rna Sequencing Of Human Peripheral Nerve In Response To Injury: Distinctive Analysis Of The Nerve Repair Pathways, Andrew S. Welleford, Jorge E. Quintero, Nader El Seblani, Eric M. Blalock, Sumedha Gunewardena, Steven M. Shapiro, Sean M. Riordan, Peter Huettl, Zain Guduru, John A. Stanford, Craig G. Van Horne, Greg A. Gerhardt

Neuroscience Faculty Publications

The development of regenerative therapies for central nervous system diseases can likely benefit from an understanding of the peripheral nervous system repair process, particularly in identifying potential gene pathways involved in human nerve repair. This study employed RNA sequencing (RNA-seq) technology to analyze the whole transcriptome profile of the human peripheral nerve in response to an injury. The distal sural nerve was exposed, completely transected, and a 1 to 2 cm section of nerve fascicles was collected for RNA-seq from six participants with Parkinson's disease, ranging in age between 53 and 70 yr. Two weeks after the initial injury, another …

Mr Perfusion Imaging, Techniques And Role In Differentiating Radiation Necrosis And Tumor Recurrence, Raima Zakaria, Fatima Mubarak, Muhammad Shahzad Shamim

Department of Radiology

High grade brain tumours are treated with surgery, chemotherapy and radiation therapy and despite such aggressive treatment, can recur in a short span of time. MRI scan has been the conventional diagnostic modality to diagnose recurrence, although at times it becomes difficult for the neuroradiologists to differentiate between tumour recurrence and radiation necrosis. Herein lies the emergent need to explore the efficacy of functional imaging to assist in this diagnostic challenge. Recent studies have sought to do so with promising implications, which we have attempted to summarize in this review.

Pediatric Brainstem Gliomas: An Institutional Experience, Altaf Ali Laghari, Mirza Zain Baig, Muhammad Ehsan Bari, Aneela Darbar, Naureen Mushtaq, Umme E Hani Abdullah, Daniya Aziz Khan

Section of Neurosurgery

Objective: The aim of this study was to analyze the clinical profiles and outcomes of pediatric brainstem gliomas treated at our institute.
Methodology: We reviewed the files of 18 pediatric age group patients diagnosed with brainstem glioma at our institution. The following variables were recorded: age, sex, duration of symptoms, date of diagnosis, main clinical symptoms, Karnofsky performance status score, magnetic resonance imaging findings, histopathology findings, details of the treatment given, disease progression, and date of mortality/last follow-up. This data were then transferred to SPSS version 23 which was used for further analysis.
Results: The mean age of our cohort …

Interleukin 1 Alpha Administration Is Neuroprotective And Neuro-Restorative Following Experimental Ischemic Stroke, Kathleen E. Salmeron, Michael E. Maniskas, Danielle N. Edwards, Raymond Wong, Ivana Rajkovic, Amanda L. Trout, Abir A. Rahman, Samantha Hamilton, Justin F. Fraser, Emmanuel Pinteaux, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Stroke remains a leading cause of death and disability worldwide despite recent treatment breakthroughs. A primary event in stroke pathogenesis is the development of a potent and deleterious local and peripheral inflammatory response regulated by the pro-inflammatory cytokine interleukin-1 (IL-1). While the role of IL-1β (main released isoform) has been well studied in stroke, the role of the IL-1α isoform remains largely unknown. With increasing utilization of intravenous tissue plasminogen activator (t-PA) or thrombectomy to pharmacologically or mechanically remove ischemic stroke causing blood clots, respectively, there is interest in pairing successful cerebrovascular recanalization with neurotherapeutic pharmacological interventions (Fraser et …

Multiple Sclerosis Outcomes After Cancer Immunotherapy, Catherine R. Garcia, Rani Jayswal, Val R. Adams, Lowell B. Anthony, John L. Villano

Markey Cancer Center Faculty Publications

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

RESULTS: We identified 14 cases of MS …

Current Management Of Glioma In Pakistan, Umme E Hani Abdullah, Altaf Ali Laghari, Muhammad Usman Khalid, Huzaifa Bin Rashid, Fatima Ali, Adnan Jabbar, Asim Hafiz, Muhammad Shahzad Shamim, Ather Enam

Section of Neurosurgery

To date, information on the management of specific neurosurgical tumors, such as glioma, in Pakistan remains scattered and scarce. Our review synthesizes the predicaments of glioma management routinely presented to the neurosurgery, medical oncology, radiation oncology, and radiology departments in Pakistan. Expert opinions were integrated from each of the relevant fields in the form of personal citations. The data presented in our review were collected from various PubMed and non-PubMed indexed articles, coupled with various health reports from the Government of Pakistan along with the World Health Organization. Through these data, it was postulated that the utilization of innovative and …

Pituitary Adenoma With Calcifications: A Case Report, Yakoot Khan, Noor Malik, Saba Iqbal Awan, Syed Hassan Khalid, Altaf Ali Laghari

Section of Neurosurgery

Pituitary adenomas and Rathke’s cleft cyst with calcification are rarely seen and craniopharyngioma still remains the common sellar suprasellar space occupying lesion with calcification. Presence of calcification is reported in pituitary adenoma in only 0.2% to 8% cases. The pituitary adenoma with calcification is a rare radiological finding and it must be distinguished from other lesions of the pituitary gland as the management and prognosis differs significantly. We report a case of a 29-year-old gentleman presented electively with the complaints of deterioration of vision for four months. CT-scan without contrast examination revealed pituitary adenoma with calcification. The patient underwent transsphenoidal …

Timing Of Postoperative Magnetic Resonance Imaging (Mri) Following Glioma Resection: Shattering The 72 Hour Window, Syed Sarmad Bukhari, Muhammad Shahzad Shamim, Fatima Mubarak

Section of Neurosurgery

Extent of enhancing tumour resection is correlated with progression free survival following glioma surgery. Historically, a contrast enhanced MRI has been recommended within 72 hours following surgery to evaluate for residual disease. This theoretical window was established amidst conflicting evidence to avoid reactive enhancement. Recent studies with better designs and better imaging quality have sought to challenge this window with a more pragmatic method of evaluating residual disease.

Emergency Care Surveillance And Emergency Care Registries In Low-Income And Middle-Income Countries: Conceptual Challenges And Future Directions For Research, Hani Mowaf, Christine Ngaruiya, Gerard O'Reilly, Olive Kobusingye, Vikas Kapil, Andres Rubiano, Marcus Ong, Juan Carlos Puyana, Akm Fazlur Rahman, Rashid Jooma, Blythe Beecrof, Junaid Razzak

Section of Neurosurgery

Despite the fact that the 15 leading causes of global deaths and disability-adjusted life years are from conditions amenable to emergency care, and that this burden is highest in low-income and middle-income countries (LMICs), there is a paucity of research on LMIC emergency care to guide policy making, resource allocation and service provision. A literature review of the 550 articles on LMIC emergency care published in the 10-year period from 2007 to 2016 yielded 106 articles for LMIC emergency care surveillance and registry research. Few articles were from established longitudinal surveillance or registries and primarily composed of short-term data collection. …

Endoscopic Transsphenoidal Surgery For Cushing's Disease: A Review, Mirza Zain Baig, Altaf Ali Laghari, Aneela Darbar, Umme E Hani Abdullah, Sumiya Abbasi

Section of Neurosurgery

Ever since the 1960s, transsphenoidal surgery has been the modality of choice for treating Cushing's disease. Subsequent visualization of the pituitary fossa and sphenoid sinus may be done either with the operating microscope or with the relatively new endoscope. The endoscope due to its panoramic view allows greater visualization as compared to the operating microscope. It confers greater access to the cavernous sinus, sella, suprasellar, and parasellar regions and accommodates higher magnifications. It is bi-dimensional, however as opposed to the operating microscope that provides a three-dimensional view and allows greater depth perception. This article provides a comprehensive review of the …

Effect Of Pregnancy On Growth Of Intracranial Meningiomas, Ayesha Quddusi, Muhammad Shahzad Shamim, Quratulain Virani

Section of Neurosurgery

Meningiomas are the most common benign primary intracranial tumours in adults. Their rapid growth during pregnancy has been well reported. Moreover, the relationship of increased progesterone expression during pregnancy and extensive tumour growth has been debated. In this review, we discuss not only the effect of progesterone on meningiomal growth but also other mechanisms involved in gestational meningiomas.