Medicine and Health Sciences Commons^™

Three-Dimensional Neurorehabilitation: A Different Perspective, Ahmad Zaheer Qureshi, Randolph Mitchell Jenkins

Pakistan Journal of Neurological Sciences (PJNS)

The authors have narrated their perspective on rehabilitation of neurological disabilities based upon their experiences in three different regions of the globe, hence the word "three dimensional". It also reflects the need of holistic approach in neurorehabilitation. The article emphasizes the significance of impact of socio-cultural factors on disability and the way different challenges can change outcomes of the same neurological impairment in different health care systems. The understanding, perception and management of disability secondary to any neurological impairment varies greatly from one region to another across the world. Hence treatment guidelines applicable in one socioeconomic setup may not be …

Improved Sensitivity To Fluorescence For Cancer Detection In Wide-Field Image-Guided Neurosurgery, Michael Jermyn, Yoann Gosselin, Pablo A. Valdes, Mira Sibai, Kolbein Kolste

Dartmouth Scholarship

In glioma surgery, Protoporphyrin IX (PpIX) fluorescence may identify residual tumor that could be resected while minimizing damage to normal brain. We demonstrate that improved sensitivity for wide-field spectroscopic fluorescence imaging is achieved with minimal disruption to the neurosurgical workflow using an electron-multiplying charge-coupled device (EMCCD) relative to a state-of-the-art CMOS system. In phantom experiments the EMCCD system can detect at least two orders-of-magnitude lower PpIX. Ex vivo tissue imaging on a rat glioma model demonstrates improved fluorescence contrast compared with neurosurgical fluorescence microscope technology, and the fluorescence detection is confirmed with measurements from a clinically-validated spectroscopic probe. Greater PpIX …

Azithromycin Drives Alternative Macrophage Activation And Improves Recovery And Tissue Sparing In Contusion Spinal Cord Injury, Bei Zhang, William M. Bailey, Timothy J. Kopper, Michael B. Orr, David J. Feola, John C. Gensel

Spinal Cord and Brain Injury Research Center Faculty Publications

BACKGROUND: Macrophages persist indefinitely at sites of spinal cord injury (SCI) and contribute to both pathological and reparative processes. While the alternative, anti-inflammatory (M2) phenotype is believed to promote cell protection, regeneration, and plasticity, pro-inflammatory (M1) macrophages persist after SCI and contribute to protracted cell and tissue loss. Thus, identifying non-invasive, clinically viable, pharmacological therapies for altering macrophage phenotype is a challenging, yet promising, approach for treating SCI. Azithromycin (AZM), a commonly used macrolide antibiotic, drives anti-inflammatory macrophage activation in rodent models of inflammation and in humans with cystic fibrosis.

METHODS: We hypothesized that AZM treatment can alter …

Pediatric Neuroradiology Pre-Call Primer, Trevor Morrison, Gilbert Vezina, Nadja Kadom

E-Learning Modules

Pediatric neuroimaging can provide a challenge to radiology residents during call due to the fact that it is infrequently encountered in many institutions. The goal of this teaching tool is to provide radiology residents with background knowledge in pediatric brain anatomy and pathology in preparation for taking call. There is one teaching tool and one assessment tool with answers, all three of which are in PowerPoint format. Emergency neuroradiology topics discussed in this module are sutures, skull fractures, bleeds, sulci and mass effect, cisterns, and herniations. After implementing this teaching tool at our institution with all incoming residents and fellows, …

Ependymal Tumors With Oligodendroglioma Like Clear Cells: Experience From A Tertiary Care Hospital In Pakistan, Fauzan Alam Hashmi, Muhammad Faheem Khan, Saad Akhtar Khan, Muhammad Waqas, Muhammad Ehsan Bari, Arsalan Ahmed

Section of Neurosurgery

Background: Ependymal tumors with oligodendroglioma like clear cells have never been reported from Pakistan. We aimed to see the features and outcomes of this rare entity.
Methods: It was retrospective cohort conducted at the Department of Neurosurgery, Aga Khan University from 2003 to 2013. The medical records and radiology of patients with proven histopathology were reviewed. Analysis was done on SPSS 20.
Results: Eleven cases of ependymal tumors with clear cells were found, which equated to 1.5% of the total tumor burden in 11 years. The median age was 49 years. Most common presenting symptom was headache 54.5%. Out of …

Emerging Immunopharmacological Targets In Multiple Sclerosis., Mojtaba Farjam, Guang-Xian Zhang, Bogoljub Ciric, Abdolmohamad Rostami

Department of Neurology Faculty Papers

Inflammatory demyelination of the central nervous system (CNS) is the hallmark of multiple sclerosis (MS), a chronic debilitating disease that affects more than 2.5 million individuals worldwide. It has been widely accepted, although not proven, that the major pathogenic mechanism of MS involves myelin-reactive T cell activation in the periphery and migration into the CNS, which subsequently triggers an inflammatory cascade that leads to demyelination and axonal damage. Virtually all MS medications now in use target the immune system and prevent tissue damage by modulating neuroinflammatory processes. Although current therapies such as commonly prescribed disease-modifying medications decrease the relapse rate …

Mice Deficient In Endothelial Α5 Integrin Are Profoundly Resistant To Experimental Ischemic Stroke, Jill Roberts, Leon De Hoog, Gregory J. Bix

Sanders-Brown Center on Aging Faculty Publications

Stroke is a disease in dire need of better therapies. We have previously shown that a fragment of the extracellular matrix proteoglycan, perlecan, has beneficial effects following cerebral ischemia via the α5β1 integrin receptor. We now report that endothelial cell selective α5 integrin deficient mice (α5 KO) are profoundly resistant to ischemic infarct after transient middle cerebral artery occlusion. Specifically, α5 KOs had little to no infarct 2–3 days post-stroke, whereas controls had an increase in mean infarct volume over the same time period as expected. Functional outcome is also improved in the α5 KOs compared with controls. Importantly, no …

Loss Of Vglut3 Produces Circadian-Dependent Hyperdopaminergia And Ameliorates Motor Dysfunction And L-Dopa-Mediated Dyskinesias In A Model Of Parkinson's Disease., Christopher B. Divito, Kathy Steece-Collier, Daniel T. Case, Sean-Paul G. Williams, Jennifer A. Stancati, Lianteng Zhi, Maria E. Rubio, Caryl E. Sortwell, Timothy J. Collier, David Sulzer, Robert H. Edwards, Hui Zhang, Rebecca P. Seal

Department of Neuroscience Faculty Papers

UNLABELLED: The striatum is essential for many aspects of mammalian behavior, including motivation and movement, and is dysfunctional in motor disorders such as Parkinson's disease. The vesicular glutamate transporter 3 (VGLUT3) is expressed by striatal cholinergic interneurons (CINs) and is thus well positioned to regulate dopamine (DA) signaling and locomotor activity, a canonical measure of basal ganglia output. We now report that VGLUT3 knock-out (KO) mice show circadian-dependent hyperlocomotor activity that is restricted to the waking cycle and is due to an increase in striatal DA synthesis, packaging, and release. Using a conditional VGLUT3 KO mouse, we show that deletion …

Sialylation Of Igg Fc Domain Impairs Complement-Dependent Cytotoxicity., Isaak Quast, Christian W Keller, Michael A Maurer, John P Giddens, Björn Tackenberg, Lai-Xi Wang, Christian Münz, Falk Nimmerjahn, Marinos Dalakas, Jan D Lünemann

Department of Neurology Faculty Papers

IgG molecules exert both pro- and antiinflammatory effector functions based on the composition of the fragment crystallizable (Fc) domain glycan. Sialylated IgG Fc domains have antiinflammatory properties that are attributed to their ability to increase the activation threshold of innate effector cells to immune complexes by stimulating the upregulation of the inhibitory Fcγ receptor IIB (FcγRIIB). Here, we report that IgG Fc sialylation of human monoclonal IgG1 molecules impairs their efficacy to induce complement-mediated cytotoxicity (CDC). Fc sialylation of a CD20-targeting antibody had no impact on antibody-dependent cellular cytotoxicity and did not change the affinity of the antibody for activating …

Surveillance In The Service Of Safety, Rashid Jooma

Section of Neurosurgery

The World Report on Road Traffic Injury Prevention of 2004 recommended that the newly motorizing countries establish road injury surveillance to define the burden, identify highrisk groups, plan intervention and monitor their impact. Despite its stated importance in the literature, very few examples of sustained surveillance systems are reported from low income countries. This presentation shares the results of an urban RTI surveillance program that has been running for the past 8 years since 2007 in the emergency departments of five major hospitals in Karachi, Pakistan. We describe the process of establishing the road injury surveillance system incorporating a multi-institution …

Loss Of Glycosaminoglycan Receptor Binding After Mosquito Cell Passage Reduces Chikungunya Virus Infectivity, Amber M. Paul, Dhiraj Acharya, John F. Anderson, Faqing Huang, Fengwei Bai

Publications

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause fever and chronic arthritis in humans. CHIKV that is generated in mosquito or mammalian cells differs in glycosylation patterns of viral proteins, which may affect its replication and virulence. Herein, we compare replication, pathogenicity, and receptor binding of CHIKV generated in Vero cells (mammal) or C6/36 cells (mosquito) through a single passage. We demonstrate that mosquito cell derived CHIKV (CHIKVmos) has slower replication than mammalian cell derived CHIKV (CHIKVvero), when tested in both human and murine cell lines. Consistent with this, CHIKVmos infection in both cell lines produce less cytopathic …

Bicompartmental Decompressive Craniectomy: Report Of Two Cases, Saad Akhtar, Badar Uddin Ujjan, Muhammad Waqas, Muhammad Waqas Khan Waqas Khan, Gohar Javed

Section of Neurosurgery

A recent study of randomized controlled trials showed favorable outcomes with use of decompressive craniectomy in managing and treating uncontrolled intracranial pressures accompanied with cerebral edema due to trauma. We present the details of bicompartmental decompressive craniectomy on two patients who presented with severe head trauma of supra- and infratentorial pathologies. The surgical management techniques and long-term follow-up are discussed in detail.

Neurofibromatosis Type 2 Patient Presenting With Medulloblastoma, Jan Kalimullah, Abdul Malik Amir Humza Sohail, Rai Shahjehan, Sabeehuddin Siddique, Muhammad Ehsan Bari

Section of Neurosurgery

Background: Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome with a frequency of 1 in 25,000 live births and a penetrance of almost 100% by the sixth decade of life. The main tumors occurring in NF2 patients are bilateral vestibular schwannomas, other peripheral, cranial and spinal nerve schwannomas, intracranial and intraspinal meningiomas, ependymomas, and gliomas.
Case description: We report the case of a 6-year-old boy who presented with a 1-month history of nausea and recurrent vomiting. Physical examination was positive for ataxic gait and left-sided facial nerve palsy. Family history was positive for NF2 in the patient's father and …

Olfactory Function In Migraine Both During And Between Attacks., Michael J. Marmura, Teshamae S Monteith, Waseem Anjum, Richard L Doty, Sarah E Hegarty, Scott W Keith

Sarah E Hegarty

INTRODUCTION: People with migraine often report being osmophobic, both during and between acute migraine attacks. It is not clear, however, whether such reports are associated with changes in olfaction such as hyperosmia, as measured by psychophysical testing. In this case-control study we quantitatively assessed olfactory identification ability, which correlates with threshold tests of olfactory acuity, in patients with migraine at baseline (no headache), during migraine episodes, and after a treated attack and compared the test scores to those of matched control subjects.

METHODS: Fifty episodic migraine subjects and 50 and sex- and age-matched controls without headache were tested. All completed …

Olfactory Acuity In Chronic Migraine: A Cross-Sectional Study., Alexander C Whiting, Michael J. Marmura, Sarah E Hegarty, Scott W. Keith

Sarah E Hegarty

OBJECTIVE/BACKGROUND: This study aims to measure olfactory acuity in chronic migraine subjects, at baseline and on migraine days, and compare to age- and sex-matched controls. Olfactory impairment is common in neurological disorders. While smell hypersensitivity has been established with chronic migraine, olfactory acuity has not been well studied. METHODS: We recruited 50 subjects with chronic migraine from the Jefferson Headache Center and 50 age- and sex-matched controls. Using the University of Pennsylvania Smell Identification Test (UPSIT), a validated test of olfaction, olfactory acuity was measured at baseline and during a migraine for subjects, and compared to controls at baseline and …

Caffeine And Progression Of Parkinson Disease: A Deleterious Interaction With Creatine., David K. Simon, Cai Wu, Barbara C. Tilley, Anne-Marie Wills, Michael J. Aminoff, Jacquelyn Bainbridge, Robert A. Hauser, Jay S. Schneider, Saloni Sharma, Carlos Singer, Caroline M. Tanner, Daniel Truong, Pei Shieen Wong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVE: Increased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake.

METHODS: Data were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from …

Fsd-C10: A More Promising Novel Rock Inhibitor Than Fasudil For Treatment Of Cns Autoimmunity., Yan-Le Xin, Jie-Zhong Yu, Xin-Wang Yang, Chun-Yun Liu, Yan-Hua Li, Ling Feng, Zhi Chai, Wan-Fang Yang, Qing Wang, Wei-Jia Jiang, Guang-Xian Zhang, Bao-Guo Xiao, Cun-Gen Ma

Department of Neurology Faculty Papers

Rho-Rho kinase (Rho-ROCK) triggers an intracellular signalling cascade that regulates cell survival, death, adhesion, migration, neurite outgrowth and retraction and influences the generation and development of several neurological disorders. Although Fasudil, a ROCK inhibitor, effectively suppressed encephalomyelitis (EAE), certain side effects may limit its clinical use. A novel and efficient ROCK inhibitor, FSD-C10, has been explored. In the present study, we present chemical synthesis and structure of FSD-C10, as well as the relationship between compound concentration and ROCK inhibition. We compared the inhibitory efficiency of ROCKI and ROCK II, the cell cytotoxicity, neurite outgrowth and dendritic formation, neurotrophic factors and …

The Evolution Of Epilepsy Surgery Between 1991 And 2011 In Nine Major Epilepsy Centers Across The United States, Germany, And Australia., Lara Jehi, Daniel Friedman, Chad Carlson, Gregory Cascino, Sandra Dewar, Christian Elger, Jerome Engel, Robert Knowlton, Ruben Kuzniecky, Anne Mcintosh, Terence J O'Brien, Dennis Spencer, Michael R. Sperling, Gregory Worrell, Bill Bingaman, Jorge Gonzalez-Martinez, Werner Doyle, Jacqueline French

Department of Neurology Faculty Papers

OBJECTIVE: Epilepsy surgery is the most effective treatment for select patients with drug-resistant epilepsy. In this article, we aim to provide an accurate understanding of the current epidemiologic characteristics of this intervention, as this knowledge is critical for guiding educational, academic, and resource priorities.

METHODS: We profile the practice of epilepsy surgery between 1991 and 2011 in nine major epilepsy surgery centers in the United States, Germany, and Australia. Clinical, imaging, surgical, and histopathologic data were derived from the surgical databases at various centers.

RESULTS: Although five of the centers performed their highest number of surgeries for mesial temporal sclerosis …

Iv And Ip Administration Of Rhodamine In Visualization Of Wbc-Bbb Interactions In Cerebral Vessels., Zachary Wilmer Reichenbach, Hongbo Li, John P. Gaughan, Melanie B. Elliott, Ronald Tuma

Department of Neurosurgery Faculty Papers

Epi-illuminescence intravital fluorescence microscopy has been employed to study leukocyte-endothelial interactions in a number of brain pathologies. Historically, dyes such as Rhodamine 6G have been injected intravenously. However, intravenous injections can predispose experimental animals to a multitude of complications and requires a high degree of technical skill. Here, we study the efficacy of injecting Rhodamine 6G into the peritoneum (IP) for the purpose of analyzing leukocyte-endothelial interactions through a cranial window during real time intravital microscopy. After examining the number of rolling and adherent leukocytes through a cranial window, we found no advantage to the intravenous injection (IV). Additionally, we …

Deadly Heat Wave In Karachi, July 2015: Negligence Or Mismanagement?, Adnan Salim, A. Ahmed, N. Ashraf, M. Asher

Section of Neurosurgery

No abstract provided.

Epilepsy In Pakistan: National Guidelines For Clinicians (Part 2), Fowzia Siddiqui, Shaukat Ali, Mughis Sheerani, Tipu Sultan, Shahid Mustafa, Saleem Barech, Haris Majid, Sarwar Jamil Siddiqui, Abdul Malik, Mohsin Zaheer, Wasim Akhter, Rashid Jooma

Section of Neurology

No abstract provided.

Hereditary Sensory Autonomic Neuropathy Ii, A Rare Disease In A Large Pakistani Family, Fazal M. Arain, Prem Chand

Department of Paediatrics and Child Health

Hereditary Sensory Autonomic Neuropathy II (HSAN II) is a rare genetic disorder, characterized by severe loss of pain, temperature and touch sensation. Injuries in these patients can progress to necrosis and shedding of digits and limbs. Here we report two cases of HSAN II belonging to a Pakistani family. Individual 1, a forty five year old man, had complete loss of pain sensation since birth. Self-mutilation and complication of injuries resulted in the shedding of all the digits and right foot and surgical amputation of left leg. Individual 2, a five year old girl,had delay in healing of wounds and …

A Randomized Controlled Behavioral Intervention Trial To Improve Medication Adherence In Adult Stroke Patients With Prescription Tailored Short Messaging Service (Sms)-Sms4stroke Study., Ayeesha Kamran Kamal, Quratulain Shaikh,, Omrana Pasha, Iqbal Azam Syed, Muhammad Islam,, Adeel Ali Memon, Hasan Rehman, Masood Ahmed Akram,, Muhammad Affan, Sumaira Nazir, Salman Aziz, Muhammad Jan, Anita Andani, Abdul Muqeet, Bilal Ahmed, Shariq Khoja

Department of Medicine

Background: The effectiveness of mobile technology to improve medication adherence via customized Short Messaging Service (SMS) reminders for stroke has not been tested in resource poor areas. We designed a randomized controlled trial to test the effectiveness of SMS on improving medication adherence in stroke survivors in Pakistan.

Methods: This was a parallel group, assessor-blinded, randomized, controlled, superiority trial. Participants were centrally randomized in fixed block sizes. Adult participants on multiple medications with access to a cell phone and stroke at least 4 weeks from onset (Onset as defined by last seen normal) were eligible. The intervention group, in addition …

Initial Validation Of A Novel Method Of Presurgical Language Localization Through Functional Connectivity (Fcmri), Stephanie M. Noble, Dustin Scheinost, Susan Y. Bookheimer, Patricia Walshaw, R Todd Constable, Christopher F. Benjamin

Yale Day of Data

OBJECTIVE: Neurosurgery is potentially curative in chronic epilepsy but can only be offered to patients if the surgical risk to language is known. Clinical functional magnetic resonance imaging (fMRI) is an ideal, noninvasive method for localizing language cortex yet remains to be validated for this purpose. We have recently presented a novel method for localizing language cortex. Here we present a preliminary evaluation of this method’s validity. We hypothesized language regions identified using this novel method would demonstrate stronger functional connectivity than randomly generated set of proximal networks. METHOD: fMRI data were collected from sixteen temporal lobe patients …

Frontal Gray Matter Abnormalities Predict Seizure Outcome In Refractory Temporal Lobe Epilepsy Patients, Gaelle Eve Doucet, Xiaosong He, Michael R Sperling, Ashwini Sharan Md, Joseph I. Tracy

Department of Neurology Faculty Papers

This article has been peer reviewed. It was published in: NeuroImage: Clinical. Volume 9, 2015, Pages 458-466.

The published version is available at DOI: 10.1016/j.nicl.2015.09.006

Copyright © 2015 The Authors.

Gm1 Ganglioside In Parkinson's Disease: Pilot Study Of Effects On Dopamine Transporter Binding., Jay S. Schneider, Franca Cambi, Stephen M. Gollomp, Hiroto Kuwabara, James R. Brašić, Benjamin E. Leiby, Stephanie Sendek, Dean F. Wong

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVE: GM1 ganglioside has been suggested as a treatment for Parkinson's disease (PD), potentially having symptomatic and disease modifying effects. The current pilot imaging study was performed to examine effects of GM1 on dopamine transporter binding, as a surrogate measure of disease progression, studied longitudinally.

METHODS: Positron emission tomography (PET) imaging data were obtained from a subset of subjects enrolled in a delayed start clinical trial of GM1 in PD [1]: 15 Early-start (ES) subjects, 14 Delayed-start (DS) subjects, and 11 Comparison (standard-of-care) subjects. Treatment subjects were studied over a 2.5 year period while Comparison subjects were studied over 2 …

A Multiscale Mapping Assessment Of Lake Champlain Cyanobacterial Harmful Algal Blooms, Nathan Torbick, Megan Corbiere, Yu-Pin Lin

Dartmouth Scholarship

Lake Champlain has bays undergoing chronic cyanobacterial harmful algal blooms that pose a public health threat. Monitoring and assessment tools need to be developed to support risk decision making and to gain a thorough understanding of bloom scales and intensities. In this research application, Landsat 8 Operational Land Imager (OLI), Rapid Eye, and Proba Compact High Resolution Imaging Spectrometer (CHRIS) images were obtained while a corresponding field campaign collected in situ measurements of water quality. Models including empirical band ratio regressions were applied to map chlorophylla and phycocyanin concentrations; all sensors performed well with R² and root-mean-square error (RMSE) ranging …

Behavioral And Morphological Parameters Of Neurons Predict The Inhibitory Potential Of Cspg Motifs: A Novel Technique, Edward Matin Kobraei

Kaleidoscope

Our lab aims to systematically identify the structural elements of chondroitin sulfate proteoglycans (CSPGs) that inhibit regeneration following spinal cord injury (SCI). CSPGs are extracellular matrix molecules produced by astrocytes of glial scar tissue following SCI. Central to this project is the use of CSPGs referred to as “Designer PGs,” which contain engineered modifications in the GAG chains and/ or the protein core of the neural CSPG aggrecan. Using established bioassays in vitro, we qualitatively and quantitatively measure growth cone behaviors and morphology as they interact with Designer PG molecules. These measurements are then translated into a composite inhibitory quotient …

Human Ips Cell-Derived Astrocyte Transplants Preserve Respiratory Function After Spinal Cord Injury., Ke Li, Elham Javed, Daniel Scura, Tamara J. Hala, Suneil Seetharam, Aditi Falnikar, Jean-Philippe Richard, Ashley Chorath, Nicholas J. Maragakis, Megan C. Wright, Angelo C. Lepore

Department of Neuroscience Faculty Papers

Transplantation-based replacement of lost and/or dysfunctional astrocytes is a promising therapy for spinal cord injury (SCI) that has not been extensively explored, despite the integral roles played by astrocytes in the central nervous system (CNS). Induced pluripotent stem (iPS) cells are a clinically-relevant source of pluripotent cells that both avoid ethical issues of embryonic stem cells and allow for homogeneous derivation of mature cell types in large quantities, potentially in an autologous fashion. Despite their promise, the iPS cell field is in its infancy with respect to evaluating in vivo graft integration and therapeutic efficacy in SCI models. Astrocytes express …

Muscle Weakness During Aging: A Deficiency State Involving Declining Angiogenesis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

This essay begins by proposing that muscle weakness of old age from sarcopenia is due in large part to reduced capillary density in the muscles, as documented in 9 reports of aged persons and animals. Capillary density (CD) is determined by local levels of various angiogenic factors, which also decline in muscles with aging, as reported in 7 studies of old persons and animals. There are also numerous reports of reduced CD in the aged brain and other studies showing reduced CD in the kidney and heart of aged animals. Thus a waning angiogenesis throughout the body may be …