Neurosurgery Commons^™

A Hallmark Clinical Study Of Cord Blood Therapy In Adults With Ischemic Stroke, Paul R. Sanberg, Jared Ehrhart

Neurosurgery and Brain Repair Faculty Publications

The therapeutic application of human umbilical cord blood cells has been an area of great interest for at least the last 25 years. Currently, cord blood cells are approved for reconstitution of the bone marrow following myeloablation in both young and old patients with myeloid malignancies and other blood cancers. Translational studies investigating alternative uses of cord blood have also shown that these cells not only stimulate neurogenesis in the aged brain but are also potentially therapeutic in the treatment of adult neurodegenerative disorders including amyotrophic lateral sclerosis, Alzheimer’s disease, ischemic stroke, traumatic brain injury, and Parkinson’s disease. Recent advances …

Immunomodulation With Human Umbilical Cord Blood Stem Cells Ameliorates Ischemic Brain Injury – A Brain Transcriptome Profiling Analysis, Maple L. Shiao, Ce Yuan, Andrew T. Crane, Joseph P. Voth, Mario Juliano, Laura L. Hocum Stone, Zhenghong Nan, Ying Zhang, Nicole Kuzmin-Nichols, Paul R. Sanberg, Andrew W. Grande, Walter C. Low

Neurosurgery and Brain Repair Faculty Publications

Our group previously demonstrated that administration of a CD34-negative fraction of human non- hematopoietic umbilical cord blood stem cells (UCBSC) 48 h after ischemic injury could reduce infarct volume by 50% as well as significantly ameliorate neurological deficits. In the present study, we explored possible mechanisms of action using next generation RNA sequencing to analyze the brain transcriptome profiles in rats with ischemic brain injury following UCBSC therapy. Two days after ischemic injury, rats were treated with UCBSC. Five days after administration, total brain mRNA was then extracted for RNAseq analysis using Illumina Hiseq 2000. We found 275 genes that …

Gutting The Brain Of Inflammation: A Key Role Of Gut Microbiome In Human Umbilical Cord Blood Plasma Therapy In Parkinson's Disease Model, Jea-Young Lee, Julian P. Tuazon, Jared Ehrhart, Paul R. Sanberg, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Current therapies for Parkinson's disease (PD), including L-3,4-dihydroxyphenylalanine (L-DOPA), and clinical trials investigating dopaminergic cell transplants, have generated mixed results with the eventual induction of dyskinetic side effects. Although human umbilical cord blood (hUCB) stem/progenitor cells present with no or minimal capacity of differentiation into mature dopaminergic neurons, their transplantation significantly attenuates parkinsonian symptoms likely via bystander effects, specifically stem cell graft-mediated secretion of growth factors, anti-inflammatory cytokines, or synaptic function altogether promoting brain repair. Recognizing this non-cell replacement mechanism, we examined here the effects of intravenously transplanted combination of hUCB-derived plasma into the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rat model of PD. …

Retrospective Case Series Of Traumatic Brain Injury And Post-Traumatic Stress Disorder Treated With Hyperbaric Oxygen Therapy, R. Douglas Shytle, David J. Eve, Soel-Hee Kim, Allan Spiegel, Paul R. Sanberg, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Returning veterans are frequently diagnosed with traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Considering a recent case-controlled study of hyperbaric oxygen therapy (HBOT) reporting a reduction in suicidal ideation, we investigated retrospectively three veterans with chronic TBI/PTSD symptoms who were treated with multiple rounds of HBOT with neurophysiological testing performed before and after treatment. Improvements were detected on parameters within neurocognitive domains, including reductions in suicide-related symptoms. These findings independently confirm that HBOT may be effective in treating specific symptoms of TBI/PTSD that are not currently addressed with existing therapeutic approaches.

Administration Of Rctrp9 Attenuates Neuronal Apoptosis Through Adipor1/Pi3k/Akt Signaling Pathway After Ich In Mice, Lianhua Zhao, John H. Zhang, Prativa Sherchan, Paul R. Krafft, Wei Zhao, Sa Wang, Shengpan Chen, Zaiyu Guo, Jiping Tang

Neurosurgery and Brain Repair Faculty Publications

Targeting neuronal apoptosis after intracerebral hemorrhage (ICH) may be an important therapeutic strategy for ICH patients. Emerging evidence indicates that C1q/TNF-Related Protein 9 (CTRP9), a newly discovered adiponectin receptor agonist, exerts neuroprotection in cerebrovascular disease. The aim of this study was to investigate the anti-apoptotic role of CTRP9 after experimental ICH and to explore the underlying molecular mechanisms. ICH was induced in mice via intrastriatal injection of bacterial collagenase. Recombinant CTRP9 (rCTRP9) was administrated intranasally at 1 h after ICH. To elucidate the underlying mechanisms, adiponectin receptor1 small interfering ribonucleic acid (AdipoR1 siRNA) and selective PI3 K inhibitor LY294002 were …

Pathophysiology Of Ganglioside Gm1 In Ischemic Stroke: Ganglioside Gm1: A Critical Review, Wenchao Zhang, Paul R. Krafft, Tianlong Wang, John H. Zhang, Li Li, Jiping Tang

Neurosurgery and Brain Repair Faculty Publications

Ganglioside GM1 is a member of the ganglioside family which has been used in many countries and is thought of as a promising alternative treatment for preventing several neurological diseases, including cerebral ischemic injury. The therapeutic effects of GM1 have been proved both in neonates and in adults following ischemic brain damage; however, its clinical efficacy in patients with ischemic stroke is still uncertain. This review examines the recent knowledge of the neuroprotective properties of GM1 in ischemic stroke, collected in the past two decades. We conclude that GM1 may have potential for stroke treatment, although we need to be …

Human Papillomavirus And Human Cytomegalovirus Infection And Association With Prognosis In Patients With Primary Glioblastoma In Pakistan, Syed Adnan Ali, Yumna Mirza, Zubair Ahmad, Nida Zahid, Ather Enam

Department of Surgery Docs

Objective: Glioblastoma multiforme (GBM) is the most common adult primary brain tumor. Human cytomegalovirus (HCMV) has been studied for the past decade, and conflicting results have been reported with no conclusive role established yet. Human papillomavirus (HPV) is involved in the pathogenesis of many cancers and has a high prevalence in patients with cervical and oral cancer in Pakistan. The objective of our study was to identify the prevalence of HCMV and HPV in Pakistani patients with primary GBM.
Methods: In total, 112 primary GBM biopsies were analyzed. HCMV and HPV infection was investigated using nested and conventional polymerase chain …

Frontoethmoidal Encephalocele Presenting In Concert With Schizencephaly, Asra Tanwir, Syed Sarmad Bukhari, Muhammad Shahzad Shamim

Section of Neurosurgery

Background: Schizencephaly is a rare defect which is identified as clefts that are lined with grey matter extending from the ependyma of the cerebral ventricles to the pia mater. An encephalocele occurs due to failure of neural tube closure resulting in a gap through which cerebrospinal fluid and meninges can bulge into a pouch. There have been rare instances when these two defects have presented simultaneously.
Case description: We report a case of a 17-year-old child who was brought by his parents with complaint of swelling over his nose and forehead and aggressive behavior since birth. Magnetic resonance imaging findings …

Preservation Of Hearing And Facial Nerve Function With The Microsurgical Excision Of Large Vestibular Schwannomas: Experience With The Retrosigmoid Approach, Muhammad Shaheryar Ahmed Rajput, Ahmad Nawaz Ahmad, Asif Ali Arain, Muhammad Adeel, Syed Akram, Mohammad Sohail Awan, Muhammad Ehsan Bari

Section of Neurosurgery

Introduction: Vestibular schwannomas (VS) are the most common benign neoplasms of a cerebellopontine angle (CPA), which arise from the Schwann cells of the vestibulocochlear nerve. Eighty percent of CPA tumors are VS followed by meningioma as the second common mass lesion in this critical potential space. Treatment options range from watchful waiting with serial imaging studies to radiosurgery or a microsurgical excision or a combination of surgery and radiation therapy. The primary objective of the study was to assess hearing and facial nerve status before and after the surgery via the retrosigmoid approach.
Methods: The database of Aga Khan University …

Role Of Stereotactic Radiosurgery In The Treatment Of Acromegaly, Komal Naeem, Aneela Darbar, Muhammad Shahzad Shamim

Section of Neurosurgery

Acromegaly is a rare, indolent disease due to overproduction of growth hormone. Surgery is identified as primary treatment, but has its limitation, thus frequently requiring alternate treatment options as adjunct to surgery. Stereotactic radiosurgery (SRS) has been used as adjuvant and alternate therapy in patients with inoperable or residual disease; or those not fit for surgery. It has shown reasonable results for treating macroadenoma and tumours invading cavernous sinuses with significant reduction in tumour size and durable endocrinological remission. Factors favouring better outcomes include time from last resection to SRS, older age, peri-procedural withdrawal of medication, higher margin and maximum …

Radiological And Clinical Outcomes In Patients Undergoing Anterior Cervical Discectomy And Fusion: Comparing Titanium And Peek (Polyetheretherketone) Cages, Muhammad Junaid, Mamoon Ur Rashid, Syed Sarmad Bukhari, Mamoon Ahmed

Section of Neurosurgery

Objectives: To study clinical and radiological outcomes in patients who had undergone the procedure of anterior cervical discectomy and fusion with titanium or PEEK (polyetheretherketone) cages for cervical disc prolapse.
Methods: This is a retrospective/non-randomized study which was conducted at the Combined Military Hospital Peshawar. Study interval was four years from 1st October, 2010 to 31st September, 2014. Total number of included patients were 149. All of the patients had undergone the procedure of anterior cervical discectomy and fusion with titanium or PEEK (polyetheretherketone) cages. All of the patients had plain MRI cervical spine done for diagnosis of anterior cervical …

Tumour Treating Fields (Ttfs) For Paediatric Brain Tumours, Brain Metastases And Other Novel Applications, Farhan Arshad Mirza, Muhammad Shahzad Shamim

Section of Neurosurgery

Tumour treating fields (TTFs) are now FDA approved for high grade glioma treatment. Novel application of this treatment modality is being assessed for paediatric brain tumours and intracranial metastatic disease. Clinical trials are being conducted to test the efficacy of this treatment modality as adjuvant therapy to current standard of care. Here we will discuss the existing literature on TTF its role in pathologies other than GBM. In addition, aspects of safety, compliance and cost are also discussed.

"It's A Precious Gift, Not To Waste": Is Routine Cross Matching Necessary In Orthopedics Surgery?: Retrospective Study Of 699 Patients In 9 Different Procedures, Obada Hasan, Eraj Khurshid Khan, Moiz Ali, Sadaf Sheikh, Anum Fatima, Haroon Ur Rashid

Section of Orthopaedic Surgery

Background: Orthopedic surgeries are usually associated with excessive blood loss which leads surgeons to overestimate need for blood transfusions and over ordering of blood. The cross matched blood, when not used, leads to the wastage of blood bank resources in terms of time, money and manpower. The objective of this study was to investigate the compliance to previously proposed MSBOS and to provide updated recommendations for all orthopedic procedures.
Methods: A retrospective analysis was conducted between 1st June 2015 and 31st May 2016. Patients admitted to the orthopedic surgery service for whom blood products were requested were included. Cross Match/Transfusion …

Cd133 Expression In Glioblastoma Multiforme: A Literature Review, Syed Ijlal Ahmed, Gohar Javed, Altaf Ali Laghari, Syeda Beenish Bareeqa, Saba Farrukh, Shajeeah Zahid, Syeda Sana Samar, Kashif Aziz

Section of Neurosurgery

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most common primary brain tumor. Extensive research has been carried out to discover the factors associated with the course and progression of GBM. CD133 is a glycoprotein antigen found in normal and malignant tissues. CD133 has been recognized as a marker for the growth of cancer cells. The association between this tissue marker and GBM is being investigated. The aim of this review was to evaluate the role of CD133 as a tumor marker for the prognosis of GBM.

Third Ventricular Tumors: A Comprehensive Literature Review, Syed Ijlal Ahmed, Gohar Javed, Altaf Ali Laghari, Syeda Benish Bareeqa, Kashif Aziz, Mehreen Khan, Syeda Sana Samar, Raja Azhar Humera, Alizay Rashid Khan, Muhammad Osama Farooqui, Amir Shahbaz

Section of Neurosurgery

Third ventricle tumors are uncommon and account for 0.6 - 0.9% of all the brain tumors. Tumors of the third ventricle are classified into primary tumors, such as colloid cysts, choroid plexus papillomas, and ependymomas, or secondary tumors, such as craniopharyngiomas, optic nerve gliomas, pineal tumors, and meningiomas. Third ventricular tumors are uncommon, and their treatment involves significant morbidity and mortality. The colloid cyst has a better surgical outcome and many approaches are available to achieve a complete cure. Choroid plexus papilloma is also a common tumor documented with its treatment majorly based on surgical resection. In addition to multiple …

Outcome Of Decompressive Craniectomy In Traumatic Closed Head Injury, Altaf Ali Laghari, Muhammad Ehsan Bari, Muhammad Waqas, Syed Ijlal Ahmed, Karim Rizwan Nathani, Wardah Moazzam

Section of Neurosurgery

Objective: The aim of the current study was to observe functional outcomes of patients undergoing decompressive craniectomy (DC) for raised intracranial pressure (ICP) after blunt head injury and to assess possible predictive factors.
Methodology: This study was a prospective cohort study which was conducted at Aga Khan University Hospital, Karachi over a period of 2 years (January 2015-December 2016). Adult patients, aged between 15 and 65 years of both genders undergoing DC during the study period were selected. Outcomes of DC were assessed at an interval of 3 months following injury using the Glasgow outcome score. The data were analyzed …

Tumour Treating Fields (Ttfs) For Recurrent And Newly Diagnosed Glioblastoma Multiforme, Farhan Ahmed, Muhammad Shahzad Shamim

Section of Neurosurgery

In the last decade, significant advances have been made in Glioblastoma Multiforme treatment with the novel use of alternating electrical fields, also termed as tumour treating fields (TTFs). This modality has shown promising results in recurrent and newly diagnosed GBM patients, and according to some, may soon be considered an addition to the previously known 'trifecta' of GBM standard of care, i.e., surgery, chemo and radiation therapy.Here we review the existing data on TTF for both recurrent and newly diagnosed GBM. This review does not discuss the limitations of TTF, especially from compliance and cost point of view.

Strategies To Increase Early Discharges To Decrease Hospital Length Of Stay And Avoidable Patient Days For Neuro-Spine Patients, Corey Fravert, Joy Moody, Mark Parker, Suneela Nayak, Stephen Tyzik, Ruth Hanselman, Amy Sparks

Operations Transformation

STRATEGIES TO INCREASE MORNING DISCHARGES IN AN ACADEMIC TERTIARY HOSPITAL

Delays in patient discharge result in numerous negative impacts on the health care system. Amongst those are a reduced patient flow and satisfaction, long wait times, and physician/ staff frustration.

An inpatient neurotrauma unit initiated a performance improvement project that utilized a multidisciplinary approach to identify barriers to discharge and coordinate a discharge plan focused on neurospine patients.

A root cause analysis was conducted to collect reasons that these patients were not discharged by 11:00am. As a result of the findings, 4 performance improvement plans were created. Subsequent data collection …

Translational Evaluation Of Acid/Base And Electrolyte Alterations In Rodent Model Of Focal Ischemia, Sarah R. Martha, Lisa A. Collier, Stephanie M. Davis, Hilary A. Seifert, Christopher C. Leonardo, Craig T. Ajmo, Elspeth A. Foran, Justin F. Fraser, Keith R. Pennypacker

Neurology Faculty Publications

BACKGROUND AND PURPOSE: Acid/base and electrolytes could provide clinically valuable information about cerebral infarct core and penumbra. We evaluated associations between acid/base and electrolyte changes and outcomes in 2 rat models of stroke, permanent, and transient middle cerebral artery occlusion.

METHODS: Three-month old Sprague-Dawley rats underwent permanent or transient middle cerebral artery occlusion. Pre- and post-middle cerebral artery occlusion venous samples for permanent and transient models provided pH, carbon dioxide, oxygen, glucose, and electrolyte values of ionized calcium, potassium, and sodium. Multiple regression determined predictors of infarct volume from these values, and Kaplan-Meier curve analyzed morality between permanent and transient …

Tranexamic Acid For Significant Traumatic Brain Injury (The Crash-3 Trial): Statistical Analysis Plan For An International, Randomised, Double-Blind, Placebo-Controlled Trial, Ian Roberts, Antonio Belli, Amy Brenner, Rizwana Chaudhri, Bukola Fawole, Tim Harris, Rashid Jooma, Abda Mahmood, Temitayo Shokunbi, Haleema Shakur, Crash-3 Trial Collaborators

Section of Neurosurgery

Background: Worldwide, traumatic brain injury (TBI) kills or hospitalises over 10 million people each year. Early intracranial bleeding is common after TBI, increasing the risk of death and disability. Tranexamic acid reduces blood loss in surgery and death due to bleeding in trauma patients with extra-cranial injury. Early administration of tranexamic acid in TBI patients might limit intracranial bleeding, reducing death and disability. The CRASH-3 trial aims to provide evidence on the effect of tranexamic acid on death and disability in TBI patients. We will randomly allocate about 13,000 TBI patients (approximately 10,000 within 3 hours of injury) to an …