Medical Specialties Commons^™

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 …

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 …

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 …

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 …

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 …

Csf And Blood Levels Of Gfap In Alexander Disease(1,2,3)., Paige L Jany, Guillermo E Agosta, William S Benko, Jens C Eickhoff, Stephanie R Keller, Adeline Vanderver, +13 Additional Authors

Neurology Faculty Publications

Alexander disease is a rare, progressive, and generally fatal neurological disorder that results from dominant mutations affecting the coding region of GFAP, the gene encoding glial fibrillary acidic protein, the major intermediate filament protein of astrocytes in the CNS. A key step in pathogenesis appears to be the accumulation of GFAP within astrocytes to excessive levels. Studies using mouse models indicate that the severity of the phenotype correlates with the level of expression, and suppression of GFAP expression and/or accumulation is one strategy that is being pursued as a potential treatment. With the goal of identifying biomarkers that indirectly reflect …

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 …

Stroke Manifesto - What Must Be Done For Stroke Care In Pakistan, Abdul Malik, Ismail Khatri, Mohammad Wasay

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

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 …

Modifiable Risk Factors In Patients With Cerebrovascular Accident, Sher Ali Khan, Mir Jalal-Ud-Din, Raheel Ahangir Jadoon, Shawana Asad, Rashid Ali, Muhammad Saqib Saeed

Pakistan Journal of Neurological Sciences (PJNS)

To determine the frequency of modifiable risk factors of stroke. Study Design: Descriptive Case series. Place and duration of study: Ayub Teaching Hospital, Abbottabad from March to December 2012. Methodology: 106 cases of cerebrovascular accident (CVA) above 20 years of age and of either sex admitted in medical units of Ayub Teaching Hospital, Abbottabad were included in this study. The patients below 20 years of age, those with recurrent history of CVA, patients not fulfilling the required criteria of risk factors set in operational definitions and patients having intracranial space occupying lesion such as tumors or brain abscess or neurological …

Type Of Preoperative Aura May Predict Postsurgical Outcome In Patients With Temporal Lobe Epilepsy And Mesial Temporal Sclerosis., Ali Akbar Asadi-Pooya, Maromi Nei, Ashwini Sharan, Michael R. Sperling

Department of Neurology Faculty Papers

PURPOSE: As the initial symptoms of epileptic seizures, many types of auras have significant localizing or lateralizing value. In this study, we hypothesized that the type of aura may predict postsurgical outcome in patients with medically refractory temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS).

METHODS: In this retrospective study, all patients with a clinical diagnosis of medically refractory TLE due to unilateral mesial temporal sclerosis who underwent epilepsy surgery at the Jefferson Comprehensive Epilepsy Center were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups: seizure freedom or …

Fasting Headache, A Cross-Sectional Study, Adnan Salim, Muhammad Ahmed Ilyas, Mehwish Rizvi, Arzlan Ullaha Baig, Syed Hassaan Ahmed, Zuha Pandit, Muhammad Saleem Ilyas

Section of Neurosurgery

Headache is a predominant disorder in general population and is classified into primary and secondary forms by the International Headache Society. Fasting headache is currently classified in Group 10 of ICHD-III as “Headache attributed to disorders of homeostasis”. In spite of continuing research, there is still indistinctness regarding the exact cause of fasting headache. Hypoglycaemia, previous history of headache, stress, caffeine withdrawal, lack of sleep and female gender have been speculated as causative factors. Our rationale for this study is to find out what percentage of the population experiences fasting headache and to find out any link between the occurrence …

Anti-Mog Antibodies Are Frequently Associated With Steroid-Sensitive Recurrent Optic Neuritis., Konstantina Chalmoukou, Harry Alexopoulos, Sofia Akrivou, Panos Stathopoulos, Markus Reindl, Marinos C. Dalakas

Department of Neurology Faculty Papers

No abstract provided.

Prevalence Of And Risk Factors For Intracranial Abnormalities In Unprovoked Seizures., Peter S. Dayan, Kathleen Lillis, Jonathan Bennett, Gregory P. Conners, Pam Bailey, James Callahan, Cigdem Akman, Neil Feldstein, Joshua Kriger, W Allen Hauser, Nathan Kuppermann

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Prospective data are lacking to determine which children might benefit from prompt neuroimaging after unprovoked seizures. We aimed to determine the prevalence of, and risk factors for, relevant intracranial abnormalities in children with first, unprovoked seizures.

METHODS: We conducted a 6-center prospective study in children aged >28 days to 18 years with seemingly unprovoked seizures. Emergency department (ED) clinicians documented clinical findings on a standardized form. Our main outcome was the presence of a clinically relevant intracranial abnormality on computed tomography (CT) or MRI, defined as those that might change management, either emergently, urgently, or nonurgently.

RESULTS: …

Mechanisms Of Immunological Tolerance In Central Nervous System Inflammatory Demyelination., Elisabeth R. Mari, Jason N. Moore, Guang-Xian Zhang, A. M. Rostami

Department of Neurology Faculty Papers

Multiple sclerosis is a complex autoimmune disease of the central nervous system that results in a disruption of the balance between pro-inflammatory and anti-inflammatory signals in the immune system. Given that central nervous system inflammation can be suppressed by various immunological tolerance mechanisms, immune tolerance has become a focus of research in the attempt to induce long-lasting immune suppression of pathogenic T cells. Mechanisms underlying this tolerance induction include induction of regulatory T cell populations, anergy and the induction of tolerogenic antigen-presenting cells. The intravenous administration of encephalitogenic peptides has been shown to suppress experimental autoimmune encephalomyelitis and induce tolerance …

Predicting The Laterality Of Temporal Lobe Epilepsy From Pet, Mri, And Dti: A Multimodal Study., Dorian Pustina, Brian Avants, Michael R Sperling, Richard Gorniak, Xiaosong He, Gaelle Eve Doucet, Paul Barnett, Ms, Scott Mintzer, Ashwini Sharan Md, Joseph I Tracy

Department of Neurology Faculty Papers

Pre-surgical evaluation of patients with temporal lobe epilepsy (TLE) relies on information obtained from multiple neuroimaging modalities. The relationship between modalities and their combined power in predicting the seizure focus is currently unknown. We investigated asymmetries from three different modalities, PET (glucose metabolism), MRI (cortical thickness), and diffusion tensor imaging (DTI; white matter anisotropy) in 28 left and 30 right TLE patients (LTLE and RTLE). Stepwise logistic regression models were built from each modality separately and from all three combined, while bootstrapped methods and split-sample validation verified the robustness of predictions. Among all multimodal asymmetries, three PET asymmetries formed the …

Age At Onset In Patients With Medically Refractory Temporal Lobe Epilepsy And Mesial Temporal Sclerosis: Impact On Clinical Manifestations And Postsurgical Outcome., Ali Akbar Asadi-Pooya, Michael R. Sperling

Department of Neurology Faculty Papers

PURPOSE: To evaluate the demographic and clinical manifestations and postsurgical outcome of childhood-onset mesial temporal sclerosis and temporal lobe epilepsy (MTS-TLE) and establishing the potential differences as compared to the patients with adult-onset MTS-TLE.

METHOD: In this retrospective study all patients with a clinical diagnosis of medically refractory TLE due to mesial temporal sclerosis, who underwent epilepsy surgery at Jefferson comprehensive epilepsy center, were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups; seizure-free or relapsed. Clinical manifestations and outcome were compared between patients with childhood-onset MTS-TLE (i.e., age at …

Improving Medication Adherence In Stroke Patients Through Short Text Messages (Sms4stroke)-Study Protocol For A Randomized, Controlled Trial., Ayeesha Kamran Kamal, Quratulain Nauman Shaikh,, Omrana Pasha, Iqbal Azam Syed, Muhammad Islam, Adeel Ali Memon,, Hasan Rehman,, Muhammad Affan,, Sumaira Nazir, Salman Aziz,, Muhammad Jan, Anita Andani, Abdul Muqeet, Bilal Ahmed,, Shariq Khoja

Department of Medicine

Background: Stroke is a major cause of morbidity and mortality, especially in low and middle income countries. Medical management is the mainstay of therapy to prevent recurrence of stroke. Current estimates are that only 1 in 6 patients have perfect adherence to medication schedules. Using SMS (Short Messaging Service) as reminders to take medicines have been used previously for diseases such as diabetes and HIV with moderate success. We aim to explore the effectiveness and acceptability of SMS in increasing adherence to medications in patients with stroke.

Methods: This will be a randomized, controlled, assessor blinded single center superiority trial. …

Diagnostic Tcd For Intracranial Stenosis In Acute Stroke Patients: Experience From A Tertiary Care Stroke Center In Karachi, Pakistan., Ayeesha Kamran Kamal, Hasan Rehman, Nasir Mustafa, Bilal Ahmed, Mohammad Jan, Faisal Wadivalla, Syed Kamran

Department of Medicine

Background: Stroke is a common cause of morbidity and mortality around the world. Intracranial large artery atherosclerosis (ICAD) is a frequent etiology of stroke in the South Asian population. There is a need for widely available screening tools to identify patients that are at high risk of stroke due to ICAD for aggressive risk management. This study describes the experience of using the transcranial Doppler (TCD) as a screening tool for this purpose at a tertiary care hospital in a developing country.

Methods: 86 Patients admitted with stroke due to ICAD underwent TCD for six arteries (Right and left …

Sex Differences In Clinical Features Of Early, Treated Parkinson's Disease, Erika F. Augustine, Adriana Pérez, Rohit Dhall, Chizoba C. Umeh, Aleksandar Videnovic, Franca Cambi, Anne-Marie A. Wills, Jordan J. Elm, Richard M. Zweig, Lisa M. Shulman, Martha A. Nance, Jacquelyn Bainbridge, Oksana Suchowersky

Neurology Faculty Publications

INTRODUCTION: To improve our understanding of sex differences in the clinical characteristics of Parkinson's Disease, we sought to examine differences in the clinical features and disease severity of men and women with early treated Parkinson's Disease (PD) enrolled in a large-scale clinical trial.

METHODS: Analysis was performed of baseline data from the National Institutes of Health Exploratory Trials in Parkinson's Disease (NET-PD) Long-term Study-1, a randomized, multi-center, double-blind, placebo-controlled study of 10 grams of oral creatine/day in individuals with early, treated PD. We compared mean age at symptom onset, age at PD diagnosis, and age at randomization between …

Toll-Like Receptors And Dectin-1, A C-Type Lectin Receptor, Trigger Divergent Functions In Cns Macrophages, John C. Gensel, Yan Wang, Zhen Guan, Kyle A. Beckwith, Kaitlyn J. Braun, Ping Wei, Dana M. Mctigue, Phillip G. Popovich

Spinal Cord and Brain Injury Research Center Faculty Publications

Spinal cord injury (SCI) activates macrophages, endowing them with both reparative and pathological functions. The mechanisms responsible for these divergent functions are unknown but are likely controlled through stochastic activation of different macrophage receptor subtypes. Various danger-associated molecular patterns released from dying cells in the injured spinal cord likely activate distinct subtypes of macrophage pattern recognition receptors, including bacterial toll-like receptors (TLRs) and fungal C-type lectin receptors (e.g., dectin-1). To determine the in vivo consequences of activating these receptors, ligands specific for TLR2 or dectin-1 were microinjected, alone or in combination, into intact spinal cord. Both ligands elicit a florid …

Recessive Mutations In Polr1c Cause A Leukodystrophy By Impairing Biogenesis Of Rna Polymerase Iii, Isabelle Thiffault, Nicole I. Wolf, Diane Forget, Kether Guerrero, Adeline Vanderver, Cas Simons, Ryan J. Taft, +17 Additional Authors

Neurology Faculty Publications

A small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genes POLR3A and POLR3B. Here we report eight of these cases carrying recessive mutations in POLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, in POLR1C impair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is …

The Mouse That Trolled: The Long And Tortuous History Of A Gene Mutation Patent That Became An Expensive Impediment To Alzheimer's Research, Tania M. Bubela, Saurabh Vishnubhakat, Robert Cook-Deegan

Office of the Provost

This case study presents the tale of the academic discovery of a rare mutation for early-onset Alzheimer's disease that was patented by a sole inventor and licensed to a non-practicing entity (NPE), the Alzheimer's Institute of America (AIA). Our aims are (1) to relate this story about patents, research tools, and impediments to medical progress, and (2) to inform ongoing debates about how patents affect research, disposition of university inventions, and the distribution of benefits from publicly funded research. We present an account of the hunt for Alzheimer's genes, their patenting, assignment, and enforcement based on literature, litigation records and …

Multiple Cerebral Hydatid Cysts In 8-Year-Old Boy: A Case Report And Literature Review Of A Rare Presentation, Muhammad Baba Khan, Muhammad Riaz, Muhammad Ehsan Bari

Section of Neurosurgery

Background: Multiple cerebral hydatid cysts are very rare with only a few reports in the literature detailing diagnostic workup, medical management, surgical techniques, possible complications, and outcomes.
Case description: We present the case of an 8-year-old boy who presented with progressively worsening headaches, vomiting, and intermittent fever since 20 days. Diagnostic workup was performed, and magnetic resonance imaging revealed multiple intracranial cysts predominantly in the right frontal region with significant mass effect. A total of 19 intracranial cysts were removed surgically, and the child recovered uneventfully.
Conclusions: Neurosurgeons should keep hydatidosis in the list of differentials when evaluating patients with …

Hematoma Enlargement Among Patients With Traumatic Brain Injury: Analysis Of A Prospective Multicenter Clinical Trial, M Fareed K. Suri, Adnan I. Qureshi, Ahmed A. Malik, Malik M. Adil, Archie Defillo, Gregory T. Sherr

Articles

Observational studies suggest that hematomas continue to enlarge during hospitalization in patients with traumatic brain injury (TBI). There is limited data regarding factors associated with hematoma enlargement and on whether hematoma enlargement contributes directly to death and disability in patients with TBI.

We analyzed data collected as part of the Resuscitation Outcomes Consortium Hypertonic Saline and TBI Study. Hematoma enlargement was ascertained and collected as a predefined safety endpoint. We evaluated the effect of hematoma enlargement on the risk of death and disability at 6 months based on the Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or ≤4) using …