Neurology Commons^™

Use Of Ultrasonic Aspirator For Cns Tumour Resection, Noman Ahmad, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

Ultrasonic aspirator (UA), or the Cavitron Ultrasonic Aspirator (CUSA) as it is commonly referred to, utilizes ultrasonic waves of variable range of frequencies to disintegrate and excise tumours. It is developed as a substitute of bipolar diathermy; a tool commonly employed for coagulation that uses focussed electric current and may damage tissues by virtue of contact, or by the heat that it produces. Over the last 30 years, CUSA has become increasingly popular in several soft tissue surgeries, especially brain and spine tumour resection, as it allows reduction in the use of bipolar diathermy. It is assumed that CUSA improves …

The Detrimental Association Between Fear Of Falling And Motor Performance In Older Cancer Patients With Chemotherapy-Induced Peripheral Neuropathy, Gu Eon Kang, Tamiko K Murphy, Mark E Kunik, Hoda J Badr, Biruh T Workeneh, Sarvari V Yellapragada, Yvonne H Sada, Bijan Najafi

Faculty, Staff and Students Publications

BACKGROUND: Cancer patients with chemotherapy-induced peripheral neuropathy (CIPN) are at increased risk of falls and developing fear of falling (FoF). Although FoF may continue to impair motor performance and increase the risk of falling even further, this association remains unexplored in CIPN.

RESEARCH QUESTION: Does high FoF in patients with CIPN further deteriorate motor performance beyond the impairment from CIPN-related sensory deficits?

METHODS: In this secondary analysis of data collected from two clinical trials, gait parameters during habitual walking condition and postural sway parameters during 30-second quiet standing (eye-open and eyes-closed) were compared among older participants (≥ 65 years) with …

Post-Operative Seizure Control In Patients With Glioblastoma, Ummey Hani, Muhammad Ammar Haider, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

While the median survival in patients with glioblastoma has not improved significantly over the past decade, aggressive attempts have been made on palliation and improving quality of life in these patients. A confluence of two debilitating pathologies which massively distorts the normal day-to-day functioning of the patients who experience it, seizures in glioblastoma patients portends a poor prognosis. There exists a paucity of reported seizure outcomes after glioblastoma treatment in neurosurgical literature. Herein we present a review examining post-operative seizure control in patients with glioblastoma.

The Synergy Of Bet Inhibitors With Aurora A Kinase Inhibitors In Mycn-Amplified Neuroblastoma Is Heightened With Functional Tp53, Joanna S Yi, Oscar Sias-Garcia, Nicole Nasholm, Xiaoyu Hu, Amanda Balboni Iniguez, Matthew D Hall, Mindy Davis, Rajarshi Guha, Myrthala Moreno-Smith, Eveline Barbieri, Kevin Duong, Jessica Koach, Jun Qi, James E Bradner, Kimberly Stegmaier, William A Weiss, W Clay Gustafson

Faculty, Staff and Students Publications

Amplification of MYCN is a poor prognostic feature in neuroblastoma (NBL) indicating aggressive disease. We and others have shown BET bromodomain inhibitors (BETi) target MYCN indirectly by downregulating its transcription. Here we sought to identify agents that synergize with BETi and to identify biomarkers of resistance. We previously performed a viability screen of ∼1,900 oncology-focused compounds combined with BET bromodomain inhibitors against MYCN-amplified NBL cell lines. Reanalysis of our screening results prominently identified inhibitors of aurora kinase A (AURKAi) to be highly synergistic with BETi. We confirmed the anti-proliferative effects of several BETi+AURKAi combinations in MYCN-amplified NBL cell lines. Compared …

Metastatic Adenocarcinoma Of The Prostate To The Brain Initially Diagnosed As Meningioma By Craniotomy: A Case Report, Julia T. Scali, Young Son, Paul Chialastri, Thomas Mueller

Rowan-Virtua Research Day

Prostate cancer is the second leading cause of cancer death in men after lung cancer. The most common site of prostate metastasis is bone (84%), lymph node (10.6%), liver (10.2%), and thorax (9.1%), with 18.4% to multiple metastatic sites [1]. Prostate metastasis to the brain is rare, with less than 1% documented cases from M.D. Anderson Cancer Center [2]. It is estimated that 1%-6% of prostate cancer metastasis is found in post mortem examination [3]. Parenchymal brain metastasis has a mean survival of 9.2 months after discovery of brain metastasis [4]. Acute neurological symptoms of metastatic prostate cancer are observed …

Role Of Intra-Operative Ultrasound In Brain Tumour Surgeries, Mohammad Hamza Bajwa, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

The use of intra-operative ultrasound remains a largely underutilized option in brain tumour surgeries. The widespread availability of neuronavigation may be the reason why such a useful modality has become less popular even though recent advances in ultrasound technology have greatly improved its utility. The available literature also clearly shows that it offers additional advantages especially when used with neuronavigation. Herein the authors have briefly touched upon the available literature on the role of intraoperative ultrasound in brain tumour surgeries.

Intramedullary Spinal Cord Lesions In Children, Ummey Hani, Sameer Saleem Tebha, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

Paediatric intramedullary spinal cord lesions are uncommon pathologies, prone to result in dismal prognosis if not managed promptly and aggressively. While children usually present in good functional grades compared to adults, early recognition and treatment is important to improve outcomes. In this review, we present tumour demographics, patient factors, and treatment modalities of intramedullary spinal cord lesions in paediatric patients.

Complete Versus Subtotal Resection Of Paediatric Craniopharyngioma, Wardah Pervez, Saqib Kamran Bakhshi, Farhan A. Mirza, Muhammad Shahzad Shamim

Section of Neurosurgery

Optimal management of craniopharyngioma is challenging and requires multidisciplinary efforts for a successful outcome. The debate over radical versus a conservative resection followed by radiotherapy, continues. Current literature reports no difference in disease freedom and overall survival between the two surgical viewpoints, and favours conservative resection and radiotherapy, leading to lower morbidity and superior functional outcomes.

Gastroenteropancreatic Neuroendocrine Tumours: Clinicopathological Evaluation At Shifa International Hospital, Islamabad, Nadira Mamoon, Hania Naveed, Mariam Abid, Humaira Nasir, Imran Nazir Ahmad, Zujajah Hameed, Asna Haroon Khan

Department of Pathology and Laboratory Medicine

Objective: Clinicopathological features of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have rarely been studied in Pakistani population. We investigated clinical characteristics of these tumours according to updated World Health Organization (WHO) 2010 classification.
Methods: The data of Shifa International Hospital, Islamabad was retrospectively analysed for pathologically confirmed GEP-NETs from January 2013 to March 2018.
Results: One hundred and eighteen patients (mean age, 52.2± 16.4 years; Of these 65(55.1%) were males. Majority, 98(83.1%) of the patients were symptomatic including 6(5.1%) with functional tumours. Pancreas was the most frequent primary site noted in 33(28%) patients. The most common histologic type was well differentiated neuroendocrine …

Role Of Preoperative Embolization In Management Of Central Nervous System Tumours, Ummey Hani, Ahmer Nasir Baig, Muhammad Shahzad Shamim, Basit Salam

Section of Neurosurgery

Preoperative embolization plays a significant role as an adjunct to surgical intervention in the cases of certain vascular tumours of the brain. While the procedure has resulted in facilitated resection of the tumour, and has reduced morbidity and mortality, its application remains debatable within the neurosurgical community, owing to rare, but major post-procedural complications. Herein, we have reviewed the literature to assess the safety and efficacy of preoperative angiographic embolization for brain tumours.

Conservation Of Epithelial-To-Mesenchymal Transition Process In Neural Crest Cells And Metastatic Cancer, April Zhang, Hira Aslam, Neha Sharma, Aryeh Warmflash, Walid D Fakhouri

Faculty, Staff and Student Publications

Epithelial to mesenchymal transition (EMT) is a highly conserved cellular process in several species, from worms to humans. EMT plays a fundamental role in early embryogenesis, wound healing, and cancer metastasis. For neural crest cell (NCC) development, EMT typically results in forming a migratory and potent cell population that generates a wide variety of cell and tissue, including cartilage, bone, connective tissue, endocrine cells, neurons, and glia amongst many others. The degree of conservation between the signaling pathways that regulate EMT during development and metastatic cancer (MC) has not been fully established, despite ample studies. This systematic review and meta-analysis …

Intracranial Mesenchymal Tumor With Fet-Creb Fusion - A Unifying Diagnosis For The Spectrum Of Intracranial Myxoid Mesenchymal Tumors And Angiomatoid Fibrous Histiocytoma-Like Neoplasms, Emily A. Sloan, Jason Chiang, Javier E. Villanueva-Meyer, Sanda Alexandrescu, Jennifer M. Eschbacher, Wesley Wang, Manuela Mafra, Nasir Ud Din, Emily Carr-Boy, Michael Watson

Department of Pathology and Laboratory Medicine

Intracranial mesenchymal tumors with FET-CREB fusions are a recently described group of neoplasms in children and young adults characterized by fusion of a FET family gene (usually EWSR1, but rarely FUS) to a CREB family transcription factor (ATF1, CREB1, or CREM), and have been variously termed intracranial angiomatoid fibrous histiocytoma or intracranial myxoid mesenchymal tumor. The clinical outcomes, histologic features, and genomic landscape are not well defined. Here we studied twenty patients with intracranial mesenchymal tumors proven to harbor FET-CREB fusion by next-generation sequencing (NGS). The 16 female and 4 male patients had a median age of 14 years (range …

Childhood Medulloblastoma, Naureen Mushtaq, Shahzadi Resham, Muhammad Shahzad Shamim, Bilal Mazhar Qureshi, Quratulain Riaz, Eric Bouffet

Section of Haematology/Oncology

Medulloblastoma is the most common malignant brain tumour in children and is a major cause of mortality and morbidity, particularly in low- and middle-income countries. It has been risk-stratified on the basis of clinical (age, metastasis and extent of resection) and histological subtypes (classic, desmoplastic and anaplastic). However, recently medulloblastoma has been sub-grouped by using a variety of different genomic approaches, such as gene expression profiling, micro-ribonucleic acid profiling and methylation array into 4 groups, namely Wingless, Sonic hedgehog, Group 3 and Group 4. This new sub-grouping has important therapeutic and prognostic implications. After acute leukaemia, brain tumour is the …

Quality Of Life In Children Treated For Craniopharyngiomas, Mishal Gillani, Sheza Hassan, Umme Hani Abdullah, Muhammad Waqas Saeed Baqai, Muhammad Shahzad Shamim

Medical College Documents

Craniopharyngiomas are common but complex paediatric brain lesions that present interesting management challenges. Quality of life is an important consideration while choosing management options. In this review, we have discussed the existing literature on various aspects of quality of life in patients treated for craniopharyngioma, assessed by variety of measurement tools.

Conference Proceedings: Aurora Scientific Day 2020

Journal of Patient-Centered Research and Reviews

Abstracts published in this supplement were among those presented at the 46th annual Aurora Scientific Day research symposium, held virtually on May 20, 2020. The symposium provides a forum for describing research studies conducted by faculty, fellows, residents, and allied health professionals affiliated with Wisconsin-based Aurora Health Care, a part of the Advocate Aurora Health health system, which publishes the Journal of Patient-Centered Research and Reviews.

Presence And Distress Of Chemotherapy-Induced Peripheral Neuropathy Symptoms In Upper Extremities Of Younger And Older Breast Cancer Survivors, Susan Storey, Andrea Cohee, Diane Von Ah, Eric Vachon, Noah R. Zanville, Patrick O. Monahan, Timothy E. Stump, Victoria L. Champion

Journal of Patient-Centered Research and Reviews

Purpose: The purposes of this study were to determine whether the presence of upper extremity chemotherapy-induced peripheral neuropathy (CIPN) symptoms (burning, pins/needles, numbness, pain, and skin crawls) among breast cancer survivors (BCS) varied according to age (≤45 years or 55–70 years) and to examine age group differences in upper extremity CIPN symptom distress.

Methods: The study was a secondary analysis of younger (n = 505) and older (n = 622) BCS. Inclusion criteria were age of ≤45 years or 55–70 years; patient at 3–8 years postdiagnosis; patient received the chemotherapy regimen of paclitaxel, doxorubicin, and cyclophosphamide; and patient did not …

Surgical Outcomes Of Intramedullary Spinal Cord Ependymomas, Ummey Hani, Muhammad Waqas Saeed Baqai, Muhammad Shahzad Shamim

Section of Neurosurgery

Intramedullary Spinal Cord Ependymomas (ISCE) are uncommon pathologies that need to be aggressively managed before clinical deterioration sets in. Novel application of different therapeutic strategies is being assessed for improving long-term outcomes in patients presenting with these rare neoplasms. In this review, we have discussed the existing literature on ISCEs, and the role of surgery in determining outcomes in terms of neurological status, progression-free survival (PFS) and overall survival (OS).

Cerebellar Mutism Syndrome After Surgical Resection Of Posterior Fossa Neoplastic Lesions, Saqib Kamran Bakhshi, Rida Mitha, Naureen Mushtaq, Muhammad Shahzad Shamim

Section of Neurosurgery

Cerebellar Mutism Syndrome (CMS) is a well-described clinical entity that complicates surgeries for posterior fossa tumours; more so in children than adults. This review focuses on the current understanding of CMS, its incidence and risk factors. Incidence showed a variable range in retrospective studies due to variety of definitions. Risk factors can be classified as either modifiable including surgical technique, or non-modifiable which include tumour related factors. A positive correlation has been associated between tumour pathology, brain stem invasion and size of tumour at time of presentation with development of CMS.

Value Of Achieving A Watertight Dural Closure, And The Use Of Dural Sealants After Supratentorial Cranial Surgery, Ummey Hani, Fatima Aziz, Muhammad Shahzad Shamim

Section of Neurosurgery

Dural closure at the end of cranial surgery is considered an extremely important step to maintain anatomical continuity, separate the intradural space with the extradural one, and to prevent possible complications related to cerebrospinal fluid leak. Wherein its usefulness in posterior fossa craniotomy is established, many surgeons do not perform it routinely in supratentorial craniotomies, citing unnecessary delay and lack of evidence supporting it. Herein, we have reviewed the data to find evidence in support of watertight suture based dural closures compared to other dural closure techniques, in supratentorial craniotomies.

Significance Of Micro-Rna Expression In Patients With Meningioma, Rida Mitha, Muhammad Shahzad Shamim

Section of Neurosurgery

Recent brain tumour research has shown abnormalities in gene expression as key features for almost all common brain tumours investigated. However, there is increasing evidence that epigenetic abnormalities are also crucial for tumorigenesis. Epigenetic abnormalities are heritable alterations affecting gene expression without changing the primary DNA sequence. Epigenetic abnormalities in meningiomas include abnormal microRNA expression, altered DNA methylation and histone and chromatin modifications. In this review we identify the role of altered expression of microRNA in the development and recurrence of meningioma. Based on the review of current literature, extensive knowledge of micro-RNA expression cannot only determine tumour recurrence and …

Permanent Pre-Operative Cerebrospinal Fluid Diversion In Paediatric Patients With Posterior Fossa Tumours, Ummey Hani, Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

Management options for obstructive hydrocephalus in children with posterior fossa tumours have been debated upon throughout the course of neurosurgical practice. Permanent pre-operative CSF diversion via ventricular shunts or endoscopic third ventriculostomy have been employed to prevent the possible persistence of hydrocephalus after tumour removal, but is considered unnecessary and even dangerous amongst a large group of neurosurgeons. In this paper, we have reviewed the literature for the merits and demerits of pre-operative permanent CSF diversion in paediatric patients presenting with posterior fossa tumours.

Steriotactic Radiosurgery For Vestibular Schwannomas, Ummey Hani, Dr Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

The approach to treating vestibular schwannomas ranges from wait-and-scan policies to micro-and radiosurgery. However, in the past few decades, Stereotac tic Radiosurgery (SRS) has emerged as an approved primary treatment option as well. In this review, we have assessed some of the existing literature on the role of SRS in the management of vestibular schwannomas, and to estimate its efficacy in tumour control and conservation of cranial nerve function.

Primary Intracranial Malignant Melanoma, Ummey Hani, Dr Saqib Kamran Bakhshi, Muhammad Shahzad Shamim

Section of Neurosurgery

Primary intracranial malignant melanoma (PIMM) are rare brain tumours; more infrequent than melanomas metastasizing to the brain or those extending to the brain from adjacent structures such as the orbit. Complete surgical excision with adjuvant chemotherapy and radiation remains the mainstay of treatment. Herein, we have reviewed the literature to find the treatment modalities for PIMMs that can lead to longer overall survivals and better patient outcomes.

Small Cell Lung Cancer Presenting With Personality Change, Brian F. King, Heidi Horstman, Katherine Rizzolo

Journal of Maine Medical Center

Introduction: Paraneoplastic limbic encephalitis is a syndrome characterized by autoimmune inflammation of the limbic system in the setting of underlying malignancy. The syndrome presents with acute to subacute neuropsychiatric clinical findings, often before the cancer diagnosis is known.

Clinical Findings: A 57-year-old woman with a 30 pack-year smoking history presented to Maine Medical Center after multiple generalized tonic-clonic seizures. Her family reported periodic odd behavior including confusion, disinhibition, and paranoia--all of which preceded her first seizure by two weeks.

Diagnoses, interventions, and outcomes: MRI brain showed T2/FLAIR signal hyperintensity of the right amygdala and hippocampus with sparing of the right …

Machine Learning Prediction Of Glioblastoma Patient One-Year Survival, Andrew Du '20, Warren Mcgee, Jane Y. Wu

Student Publications & Research

Glioblastoma (GBM) is a grade IV astrocytoma formed primarily from cancerous astrocytes and sustained by intense angiogenesis. GBM often causes non-specific symptoms, creating difficulty for diagnosis. This study aimed to utilize machine learning techniques to provide an accurate one-year survival prognosis for GBM patients using clinical and genomic data from the Chinese Glioma Genome Atlas. Logistic regression (LR), support vector machines (SVM), random forest (RF), and ensemble models were used to identify and select predictors for GBM survival and to classify patients into those with an overall survival (OS) of less than one year and one year or greater. With …

Surgical Resection Of Convexity Meningiomas: A Single Center Retrospective Analysis, Haley Wendt, Michael Baldassari, Donald Ye, Kevin Judy

Phase 1

Introduction: Dural convexity meningiomas (CMs) are the most common primary intracranial tumors. Although surgical resection carries relatively low risk, it is necessary to quantify perioperative risks from a large patient cohort and identify factors contributing to short-term and long-term outcomes.

Methods: Patients who underwent craniotomy for resection of CMs between January 2012-December 2018 at a single large academic center were reviewed for pre-operative demographics, radiographic characteristics, and post-operative outcomes.

Results: 122 cases of CMs were identified. Common presenting symptoms included headache (39.3%), seizure (27.0%) and weakness/paralysis (18%). CMs were located over frontal, parietal, temporal, and occipital lobes in 57.4%, …

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 …

Biological Intratumoral Therapy For The High-Grade Glioma Part I: Intratumoral Delivery And Immunotoxins., Joshua Loya, Charlie Zhang, Emily J Cox, Achal Singh Achrol, Santosh Kesari

Articles, Abstracts, and Reports

Management of high-grade gliomas remains a complex challenge. Standard of care consists of microsurgical resection, chemotherapy and radiation, but despite these aggressive multimodality therapies the overall prognosis remains poor. A major focus of ongoing translational research studies is to develop novel therapeutic strategies that can maximize tumor cell eradication while minimizing collateral side effects. Particularly, biological intratumoral therapies have been the focus of new translational research efforts due to their inherent potential to be both dynamically adaptive and target specific. This two-part review will provide an overview of biological intratumoral therapies and summarize key advances and remaining challenges in intratumoral …

Biological Intratumoral Therapy For The High-Grade Glioma Part Ii: Vector- And Cell-Based Therapies And Radioimmunotherapy., Joshua Loya, Charlie Zhang, Emily J Cox, Achal Singh Achrol, Santosh Kesari

Articles, Abstracts, and Reports

Management of high-grade gliomas (HGGs) remains a complex challenge with an overall poor prognosis despite aggressive multimodal treatment. New translational research has focused on maximizing tumor cell eradication through improved tumor cell targeting while minimizing collateral systemic side effects. In particular, biological intratumoral therapies have been the focus of novel translational research efforts due to their inherent potential to be both dynamically adaptive and target specific. This two part review will provide an overview of biological intratumoral therapies that have been evaluated in human clinical trials in HGGs, and summarize key advances and remaining challenges in the development of these …

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 …