Medicine and Health Sciences Commons^™

Unsupervised Machine Learning Using K-Means Identifies Radiomic Subgroups Of Pediatric Low-Grade Gliomas That Correlate With Key Molecular Markers, Debanjan Haldar, Anahita Fathi Kazerooni, Sherjeel Arif, Ariana Familiar, Rachel Madhogarhia, Nastaran Khalili, Sina Bagheri, Hannah Anderson, Ibraheem Salman Shaikh, Aria Mahtabfar, Meen Chul Kim, Wenxin Tu, Jefferey Ware, Arastoo Vossough, Christos Davatzikos, Phillip B Storm, Adam Resnick, Ali Nabavizadeh

Department of Neurosurgery Faculty Papers

Introduction: Despite advancements in molecular and histopathologic characterization of pediatric low-grade gliomas (pLGGs), there remains significant phenotypic heterogeneity among tumors with similar categorizations. We hypothesized that an unsupervised machine learning approach based on radiomic features may reveal distinct pLGG imaging subtypes.

Methods: Multi-parametric MR images (T1 pre- and post-contrast, T2, and T2 FLAIR) from 157 patients with pLGGs were collected and 881 quantitative radiomic features were extracted from tumorous region. Clustering was performed using K-means after applying principal component analysis (PCA) for feature dimensionality reduction. Molecular and demographic data was obtained from the PedCBioportal and compared between imaging subtypes.

Results: …

How To Manage The Initiation Of Apomorphine Therapy Without Antiemetic Pretreatment: A Review Of The Literature, Stuart H. Isaacson, Richard B. Dewey, Rajesh Pahwa, Daniel E. Kremens

Department of Neurology Faculty Papers

Introduction

Pretreatment with the antiemetic trimethobenzamide has been recommended practice in the United States (US) to address the risk of nausea and vomiting during initiation of apomorphine treatment. However, trimethobenzamide is no longer being manufactured in the US, and despite the recent update to the US prescribing information, there may be uncertainty regarding how to initiate apomorphine.

Methods

To better understand why antiemetic pretreatment was recommended and if it is necessary when initiating apomorphine therapy, we performed a literature review of subcutaneous apomorphine therapy initiation with and without antiemetic pretreatment in patients with PD.

Results

Three studies were identified as …

Gata1 Controls Numbers Of Hematopoietic Progenitors And Their Response To Autoimmune Neuroinflammation, Daniel Hwang, Larissa Ishikawa, Maryam S. Seyedsadr, Elisabeth R. Mari, Ezgi Kasimoglu, Ziver Sahin, Alexandra Boehm, Soohwa Jang, Javad Rasouli, Courtney Vaccaro, Michael Gonzalez, Hakon Hakonarson, Mohamad Rostami, Guang-Xian Zhang, Bogoljub Ciric

Department of Neurology Faculty Papers

GATA-binding factor 1 (GATA1) is a transcription factor that governs the development and function of multiple hematopoietic cell lineages. GATA1 is expressed in hematopoietic stem and progenitor cells (HSPCs) and is essential for erythroid lineage commitment; however, whether it plays a role in hematopoietic stem cell (HSC) biology and the development of myeloid cells, and what that role might be, remains unclear. We initially set out to test the role of eosinophils in experimental autoimmune encephalomyelitis (EAE), a model of central nervous system autoimmunity, using mice lacking a double GATA-site (ΔdblGATA), which lacks eosinophils due to the deletion of the …

The Spectral Sensitivity Of Human Circadian Phase Resetting And Melatonin Suppression To Light Changes Dynamically With Light Duration, Melissa A. St Hilaire, María L. Ámundadóttir, Shadab A. Rahman, Shantha M. W. Rajaratnam, Melanie Rüger, George C. Brainard, Charles A. Czeisler, Marilyne Andersen, Joshua J. Gooley, Steven W. Lockley

Department of Neurology Faculty Papers

Human circadian, neuroendocrine, and neurobehavioral responses to light are mediated primarily by melanopsin-containing intrinsically-photosensitive retinal ganglion cells (ipRGCs) but they also receive input from visual photoreceptors. Relative photoreceptor contributions are irradiance- and duration-dependent but results for long-duration light exposures are limited. We constructed irradiance-response curves and action spectra for melatonin suppression and circadian resetting responses in participants exposed to 6.5-h monochromatic 420, 460, 480, 507, 555, or 620 nm light exposures initiated near the onset of nocturnal melatonin secretion. Melatonin suppression and phase resetting action spectra were best fit by a single-opsin template with lambda_max at 481 and 483 …

Goal Attainment After Treatment With Abobotulinumtoxina And A Tailored Home Therapy Programme In Children With Upper Limb Spasticity: Descriptive, Exploratory Analysis Of A Large Randomized, Controlled Studya, Jorge Carranza-Del Río, Nigar Dursun, Cigdem Cekmece, Marcin Bonikowski, Weronika Pyrzanowska, Edward Dabrowski, Ann Tilton, Joyce Oleszek, Magali Volteau, Simon Page, Angela Shierk, Mauricio R. Delgado

School of Medicine Faculty Publications

OBJECTIVE: This exploratory analysis of a large, randomized, double-blind study (NCT02106351) describes the effect of treatment with abobotulinumtoxinA followed by a tailored home exercises therapy programme in enabling children with upper limb spasticity due to cerebral palsy to achieve their functional goals using goal attainment scaling (GAS). METHODS: Children with cerebral palsy and spasticity in ≥ 1 upper limb received up to 4 injection cycles of abobotulinumtoxinA (2 U/kg (cycle 1 only), 8U/kg and 16U/kg) into the elbow and wrist flexors and other upper limb muscles selected to support individual treatment goals. Children followed a home exercises therapy programme, which …

Safety Of Lenadogene Nolparvovec Gene Therapy Over 5 Years In 189 Patients With Leber Hereditary Optic Neuropathy, Catherine Vignal-Clermont, Patrick Yu-Wai-Man, Nancy J. Newman, Valerio Carelli, Mark L. Moster, Valerie Biousse, Prem S. Subramanian, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Alfredo A. Sadun, Thomas Klopstock, Robert C. Sergott, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Magali Taiel, Michel Roux, José-Alain Sahel

Wills Eye Hospital Papers

Purpose

To evaluate the safety profile of lenadogene nolparvovec (Lumevoq) in patients with Leber hereditary optic neuropathy.

Design

Pooled analysis of safety data from 5 clinical studies.

Methods

A total of 189 patients received single unilateral or bilateral intravitreal injections of a recombinant adeno-associated virus 2 (rAAV2/2) vector encoding the human wild-type ND4 gene. Adverse events (AEs) were collected throughout the studies, up to 5 years. Intraocular inflammation and increased intraocular pressure (IOP) were ocular AEs of special interest. Other assessments included ocular examinations, vector bio-dissemination, and systemic immune responses against rAAV2/2.

Results

Almost all patients (95.2%) received 9 × …

Safety And Efficacy Of Salvage Therapy With Laser Interstitial Thermal Therapy For Malignant Meningioma Refractory To Cesium-131 Brachytherapy: Illustrative Case, Clifford Yudkoff, Aria Mahtabfar, Keenan Piper, Kevin Judy

Department of Neurosurgery Faculty Papers

BACKGROUND

Anaplastic meningioma are rare, cancerous tumors of the central nervous system that often require multimodal therapy for tumor control. Both laser interstitial thermal therapy (LITT) and brachytherapy with implanted cesium-131 metallic seeds have demonstrated efficacy in the treatment of recurrent and resistant anaplastic meningioma; however, their safety as a dual therapy has never been reported.

OBSERVATIONS

In this report, the authors present a case of a 53-year-old female who received LITT in combination with brachytherapy after surgical and radiation treatment options had been exhausted. The authors discuss the unique safety concern of thermal injury with this treatment combination and …

Responsive Neurostimulation (Rns) Of The Centromedian Nucleus Of The Thalamus For The Treatment Of Drug Resistant Idiopathic Generalized Epilepsy, Angelique Manasseh, Hannah Guider, Brooklynn Bondy, Ayman Haykal, Nour Baki, Ashleigh Terrell, Michael Staudt, Christopher Parres, Andrew Zillgitt

Conference Presentation Abstracts

Rationale: Idiopathic generalized epilepsy (IGE) accounts for approximately one-third of all epilepsies. The majority of people with IGE achieve seizure-freedom from treatment with anti-seizure medications (ASM). However, up to 25% of people with IGE continue to experience seizures despite adequate ASM trials. In patients with drug resistant IGE, neuromodulation with responsive neurostimulation (RNS) in the bilateral centromedian nucleus (CMN) of the thalamus may be an effective treatment option. Methods: Five patients with drug resistant IGE were evaluated through the Beaumont Adult Comprehensive Epilepsy Center and underwent an epilepsy presurgical evaluation including video-EEG monitoring in the epilepsy monitoring unit, brain MRI, …

Nursing Considerations For Post-Traumatic Amnesia After A Traumatic Brain Injury, Hannah Grant

Senior Honors Theses

A period known as post-traumatic amnesia (PTA) often follows a traumatic brain injury (TBI). PTA is characterized by anterograde and retrograde amnesia, confusion, disorientation, and agitation. The duration and severity of PTA is a key indicator of the long-term prognosis after a TBI, so proper assessment and nursing care of a PTA patient is crucial. TBIs range from mild to severe, but primarily affect the fronto-temporal lobes. In PTA, both neural lesions and white matter damage within the parahippocampal region can cause PTA. A nurse must perform a thorough assessment of a TBI patient, but, since PTA is a key …

Education Research: Neurologic Education In Physician Assistant Programs, Carl Garubba

Physician Assistant Studies | Faculty Scholarship

Background and Objectives A growing number of advanced practice providers (APPs) are entering neurologic practice, and educational initiatives focused on postgraduate training in neurology for these providers are growing in turn. Neurologic education in APP degree programs is not well defined, which limits the ability to tailor these initiatives to the specific needs of APPs. We aim to describe neurologic education in physician assistant (PA) degree programs to better inform these efforts.

Methods The 2018 American Academy of Neurology clerkship director survey was adapted for directors of PA programs via an iterative approach. The survey was distributed to program directors …

Amplification Of The Plag-Family Genes-Plagl1 And Plagl2-Is A Key Feature Of The Novel Tumor Type Cns Embryonal Tumor With Plagl Amplification, Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Nasir Uddin

Department of Pathology and Laboratory Medicine

Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0-14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal …

Impact Of Solid State Roadway Lighting On Melatonin In Humans, Ronald B Gibbons, Rajaram Bhagavathula, Benjamin Warfield, George Brainard, John P Hanifin

Department of Neurology Faculty Papers

Introduction: In 2009, the World Health Organization identified vehicle crashes, both injury-related and fatal, as a public health hazard. Roadway lighting has long been used to reduce crashes and improve the safety of all road users. Ocular light exposure at night can suppress melatonin levels in humans. At sufficient light levels, all visible light wavelengths can elicit this response, but melatonin suppression is maximally sensitive to visible short wavelength light. With the conversion of roadway lighting to solid state sources that have a greater short wavelength spectrum than traditional sources, there is a potential negative health impact through suppressed melatonin …

Improving Translatability Of Spinal Cord Injury Research By Including Age As A Demographic Variable, Andrew N. Stewart, Linda A. T. Jones, John C. Gensel

Department of Physical Therapy Faculty Papers

Pre-clinical and clinical spinal cord injury (SCI) studies differ in study design, particularly in the demographic characteristics of the chosen population. In clinical study design, criteria such as such as motor scores, neurological level, and severity of injury are often key determinants for participant inclusion. Further, demographic variables in clinical trials often include individuals from a wide age range and typically include both sexes, albeit historically most cases of SCI occur in males. In contrast, pre-clinical SCI models predominately utilize young adult rodents and typically use only females. While it is often not feasible to power SCI clinical trials to …

Delta Oscillation Coupled Propagating Fast Ripples Precede Epileptiform Discharges In Patients With Focal Epilepsy, Shennan A. Weiss, Laurent Sheybani, Nitish Seenarine, Itzhak Fried, Chengyuan Wu, Ashwini Sharan, Jerome Engel Jr., Michael R. Sperling, Yuval Nir, Richard J. Staba

Department of Neurology Faculty Papers

Epileptiform spikes are used to localize epileptogenic brain tissue. The mechanisms that spontaneously trigger epileptiform discharges are not yet elucidated. Pathological fast ripple (FR, 200–600 Hz) are biomarkers of epileptogenic brain, and we postulated that FR network interactions are involved in generating epileptiform spikes. Using macroelectrode stereo intracranial EEG (iEEG) recordings from a cohort of 46 patients we found that, in the seizure onset zone (SOZ), propagating FR were more often followed by an epileptiform spike, as compared with non-propagating FR (p < 0.05). Propagating FR had a distinct frequency and larger power (p < 1e-10) and were more strongly phase coupled to the peak of iEEG delta oscillation, which likely correspond with the DOWN states during non-REM sleep (p < 1e-8), than non-propagating FR. While FR propagation was rare, all FR occurred with the highest probability within +/− 400 msec of epileptiform spikes with superimposed high-frequency oscillations (p < 0.05). Thus, a sub-population of epileptiform spikes in the SOZ, are preceded by propagating FR that are coordinated by the DOWN state during non-REM sleep.

Study Design And Baseline Characteristics For The Reflect Gene Therapy Trial Ofm.11778g>A/Nd4-Lhon, Prem S. Subramanian, Nancy J. Newman, Mark Moster, An-Guor Wang, Patrick Yu-Wai-Man, Sean Donahue, Bart P. Leroy, Valerio Carelli, Valerie Biousse, Catherine Vignal-Clermont, Robert C. Sergott, Alfredo A. Sadun, Gema Rebolleda, Bart K. Chwalisz, Rudrani Banik, Fabienne Bazin, Eric Cox, Michel Roux, Magali Taiel, Jose-Alain Sahel

Wills Eye Hospital Papers

Objective REFLECT is the first randomised, double-masked, placebo-controlled multicentre phase 3 clinical trial that evaluated the efficacy and safety of bilateral intravitreal (IVT) injection of lenadogene nolparvovec in subjects with Leber hereditary optic neuropathy carrying the m.11778G>A mutation.

Methods and analysis A total of 98 subjects were enrolled with vision loss of ≤12 months. The subjects were randomised to one of two treatment arms with all subjects receiving an intravitreal (IVT) injection of lenadogene nolparvovec in their first affected eye and the second-affected eye randomised to receive IVT of either lenadogene nolparvovec or placebo.

Results The majority of subjects …

Individualised Prediction Of Drug Resistance And Seizure Recurrence After Medication Withdrawal In People With Juvenile Myoclonic Epilepsy: A Systematic Review And Individual Participant Data Meta-Analysis, Remi Stevelink, Dania Al-Toma, Floor E. Jansen, Herm J. Lamberink, Ali A. Asadi-Pooya, Mohsen Farazdaghi, Gonçalo Cação, Sita Jayalakshmi, Anuja Patil, Çiğdem Özkara, Şenay Aydın, Joanna Gesche, Christoph P. Beier, Linda J. Stephen, Martin J. Brodie, Gopeekrishnan Unnithan, Ashalatha Radhakrishnan, Julia Höfler, Eugen Trinka, Roland Krause, Emanuele Cerulli Irelli, Carlo Di Bonaventura, Jerzy P. Szaflarski, Laura E. Hernández-Vanegas, Monica L. Moya-Alfaro, Yingying Zhang, Dong Zhou, Nicola Pietrafusa, Nicola Specchio, Giorgi Japaridze, Sándor Beniczky, Mubeen Janmohamed, Patrick Kwan, Marte Syvertsen, Kaja K. Selmer, Bernd J. Vorderwülbecke, Martin Holtkamp, Lakshminarayanapuram G. Viswanathan, Sanjib Sinha, Betül Baykan, Ebru Altindag, Felix Von Podewils, Juliane Schulz, Udaya Seneviratne, Alejandro Viloria-Alebesque, Ioannis Karakis, Wendyl J. D'Souza, Josemir W. Sander, Bobby P. C. Koeleman, Willem M. Otte, Kees P. J. Braun

Department of Neurology Faculty Papers

BACKGROUND: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME.

METHODS: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on …

Headache Characteristics Among Patients With Epilepsy And The Association With Temporal Encephaloceles, Patricia Graese, Milad Yazdani, Zeke Campbell

Department of Neurology Faculty Papers

PURPOSE: Our aim was to determine if headaches characteristic of possible Idiopathic Intracranial Hypertension (IIH) and in general were more prevalent in patients with versus without temporal encephaloceles (TEs) among patients with epilepsy.

METHODS: Electronic medical records were reviewed retrospectively. Among 474 patients with epilepsy, 103 patients (21.7%) had at least one TE diagnosed on initial MRI or on retrospective review by a board-certified neuroradiologist, while 371 patients had no TE present. The patients were grouped into one of four categories depending on their headache characteristics (IIH-like, peri-ictal, other, or no headaches). Analysis of the categories was performed using a …

Uncovering The Biological Basis Of Control Energy: Structural And Metabolic Correlates Of Energy Inefficiency In Temporal Lobe Epilepsy, Xiaosong He, Lorenzo Caciagli, Linden Parkes, Jennifer Stiso, Teresa M. Karrer, Jason Z. Kim, Zhixin Lu, Tommaso Menara, Fabio Pasqualetti, Michael R. Sperling, Joseph I. Tracy, Dani S. Bassett

Department of Neurology Faculty Papers

Network control theory is increasingly used to profile the brain's energy landscape via simulations of neural dynamics. This approach estimates the control energy required to simulate the activation of brain circuits based on structural connectome measured using diffusion magnetic resonance imaging, thereby quantifying those circuits' energetic efficiency. The biological basis of control energy, however, remains unknown, hampering its further application. To fill this gap, investigating temporal lobe epilepsy as a lesion model, we show that patients require higher control energy to activate the limbic network than healthy volunteers, especially ipsilateral to the seizure focus. The energetic imbalance between ipsilateral and …

Human Amniotic Membrane As A Dural Substitute In Neurosurgery: A Systematic Review, Zara Shah, Saqib Kamran Bakhshi, Mohammad Hamza Bajwa, Mujtaba Khalil, Michael C. Dewan, Muhammad Shahzad Shamim

Medical College Documents

Background: Several studies have highlighted the use of human amniotic membrane (HAM) in neurosurgical procedures as an effective dural substitute. HAM has inherent antifibrotic and anti-inflammatory properties and exhibits immunomodulatory effect that makes it an ideal dural substitute. Other advantages including easy availability, low cost of procurement, and storage also render it a promising dural substitute especially in low- and middle-income countries.
Methods: A systematic literature search was performed using PubMed, Scopus, and Google Scholar databases, using the search terms "human amniotic membrane," "dural repair," and "neurosurgery." To be eligible for inclusion in our review, papers had to report primary …

What Do We Know So Far About Ofatumumab For Relapsing Multiple Sclerosis? A Meta-Analytical Study, Hafiza Munazza Taj, Maryam Talib, Sania Siddiqa, Azza Sarfraz, Zouina Sarfraz, Karla Robles-Velasco, Ivan Cherrez-Ojeda

Department of Paediatrics and Child Health

Ofatumumab is a monoclonal antibody that reduces the level of B cells that alter the progression of relapsing multiple sclerosis. Originally approved by the Food and Drug Administration (FDA) in August 2020, this meta-analysis determines the outcomes of four randomized controlled trials (RCTs) for endline outcomes of Gadolinium-enhancing T1 lesions on MRI scans reported as Cohen's d and relapse rate reported as risk ratio. All four RCTs reported favorable findings of gadolinium-enhancing T1 lesions (Cohen's d = -0.44, p < 0.00001). The relapse rate was reduced by 46% post ofatumumab administration (RR = 0.54, p < 0.00001). With 14 ongoing trials in this area, more data is required to consolidate our findings.

Amplitude Synchronization Of Spontaneous Activity Of Medial And Lateral Temporal Gyri Reveals Altered Thalamic Connectivity In Patients With Temporal Lobe Epilepsy, Anish V. Sathe, Michael Kogan, Kichang Kang, Jingya Miao, Mashaal Syed, Isaiah Ailes, Caio M. Matias, Devon Middleton, Feroze B. Mohamed, Scott Faro, Joseph Tracy, Ashwini Sharan, Mahdi Alizadeh

Department of Neurosurgery Faculty Papers

In this study, we examined whether amplitude synchronization of medial (MTL) and lateral (LTL) temporal lobes can detect unique alterations in patients with MTL epilepsy (mTLE) with mesial temporal sclerosis (MTS). This was a retrospective study of preoperative resting-state fMRI (rsfMRI) data from 31 patients with mTLE with MTS (age 23-69) and 16 controls (age 21-35). fMRI data were preprocessed based on a multistep preprocessing pipeline and registered to a standard space. Using each subject's T1-weighted scan, the MTL and LTL were automatically segmented, manually revised and then fit to a standard space using a symmetric normalization registration algorithm. Dual …

A Case Report Of Concurrent Cryptococcal And Tuberculous Meningitis In An Immunosuppressed Renal Transplant Patient, Linda Barasa, Ahmed Sokwala, Felix Riunga, Dilraj Sokhi

Internal Medicine, East Africa

Infections after renal transplant are a common cause of morbidity and are commonly due to Cytomegalovirus (CMV), Cryptococcus, Mycobacterium tuberculosis, and Aspergillus. Concurrent infections with both cryptococcal and tuberculous aetiologies are rare within the central nervous system (CNS). We present a case of a 67-year-old male patient who presented with three weeks of headaches, confusion, unsteady gait, and seizures. He had type 2 diabetes mellitus and hypertension. He had a kidney transplant three years prior and was on three immunosuppressive agents. He was HIV-negative. He was evaluated and found to have cryptococcal meningitis and received appropriate treatment with liposomal amphotericin …

Impact Of Dietary Walnuts, A Nutraceutical Option, On Circulating Markers Of Metabolic Dysregulation In A Rodent Cachectic Tumor Model, Lauri O. Byerley, Hsiao Man Chang, Brittany Lorenzen, Jessie Guidry, W. Elaine Hardman

School of Medicine Faculty Publications

Background: Nutraceutical foods, like walnuts which are rich in immunonutrients, can have medicinal benefits. Dietary walnuts have been shown to slow or prevent tumor growth in mice genetically programmed to grow breast or prostate tumors. This study investigated whether walnuts could exert the same preventable effect in a transplantable carcinoma rat model. Methods: Eighteen rats were randomly fed a diet containing walnuts (10% of food by weight), and 36 were fed a diet without walnuts (control) for 21 days. On day 22, 18 control diet rats were switched to the walnut diet. All other animals remained on their same diet. …

Association Of Noncontrast Computed Tomography And Perfusion Modalities With Outcomes In Patients Undergoing Late-Window Stroke Thrombectomy, Guilherme B F Porto, Ching-Jen Chen, Sami Al Kasab, Muhammed Amir Essibayi, Eyad Almallouhi, Zachary Hubbard, Reda Chalhoub, Ali Alawieh, Ilko Maier, Marios-Nikos Psychogios, Stacey Q Wolfe, Pascal Jabbour, Ansaar Rai, Robert M Starke, Amir Shaban, Adam Arthur, Joon-Tae Kim, Shinichi Yoshimura, Jonathan Grossberg, Peter Kan, Isabel Fragata, Adam Polifka, Joshua Osbun, Justin Mascitelli, Michael R Levitt, Richard Williamson, Daniele G Romano, Roberto Crosa, Benjamin Gory, Maxim Mokin, Kaustubh S Limaye, Walter Casagrande, Mark Moss, Ramesh Grandhi, Albert Yoo, Alejandro M Spiotta, Min S Park

Department of Neurosurgery Faculty Papers

Importance: There is substantial controversy with regards to the adequacy and use of noncontrast head computed tomography (NCCT) for late-window acute ischemic stroke in selecting candidates for mechanical thrombectomy.

Objective: To assess clinical outcomes of patients with acute ischemic stroke presenting in the late window who underwent mechanical thrombectomy stratified by NCCT admission in comparison with selection by CT perfusion (CTP) and diffusion-weighted imaging (DWI).

Design, setting, and participants: In this multicenter retrospective cohort study, prospectively maintained Stroke Thrombectomy and Aneurysm (STAR) database was used by selecting patients within the late window of acute ischemic stroke and emergent large vessel …

Neurodevelopment And Recovery From Wasting, Harriet M. Babikako, Celine Bourdon, Emmie Mbale, Peace Aber, Annet Birabwa, Josephine Chimoyo, Wieger Voskuijl, Zaubina Kazi, John Mukisa, Ali Faisal Saleem

Department of Paediatrics and Child Health

Background and objectives: Acute illness with malnutrition is a common indication for hospitalization among children in low- and middle-income countries. We investigated the association between wasting recovery trajectories and neurodevelopmental outcomes in young children 6 months after hospitalization for an acute illness.
Methods: Children aged 2 to 23 months were enrolled in a prospective observational cohort of the Childhood Acute Illness & Nutrition Network, in Uganda, Malawi, and Pakistan between January 2017 and January 2019. We grouped children on the basis of their wasting recovery trajectories using change in mid-upper arm circumference for age z-score. Neurodevelopment was assessed with the …

Genetic Testing To Inform Epilepsy Treatment Management From An International Study Of Clinical Practice, Dianalee Mcknight, Ana Morales, Kathryn E. Hatchell, Sara L. Bristow, Joshua L. Bonkowsky, Michael Scott Perry, Anne T. Berg, Felippe Borlot, Edward D. Esplin, Chad Moretz, Katie Angione, Loreto Ríos-Pohl, Robert L. Nussbaum, Swaroop Aradhya, Chad R. Haldeman-Englert, Rebecca J. Levy, Venu G. Parachuri, Guillermo Lay-Son, David J. Dávila-Ortiz De Montellano, Miguel Angel Ramirez-Garcia, Edmar O. Benítez Alonso, Julie Ziobro, Adela Chirita-Emandi, Temis M. Felix, Dianne Kulasa-Luke, Andre Megarbane, Shefali Karkare, Sarah L. Chagnon, Jennifer B. Humberson, Melissa J. Assaf, Sebastian Silva, Katherine Zarroli, Oksana Boyarchuk, Gary R. Nelson, Rachel Palmquist, Katherine C. Hammond, Sean T. Hwang, Susan B. Boutlier, Melinda Nolan, Kaitlin Y. Batley, Devraj Chavda, Carlos Alberto Reyes-Silva, Oleksandr Miroshnikov, Britton Zuccarelli, Louise Amlie-Wolf, James W. Wheless, Syndi Seinfeld, Manoj Kanhangad, Jeremy L. Freeman, Susana Monroy-Santoyo, Natalia Rodriguez-Vazquez, Monique M. Ryan, Michelle Machie, Patricio Guerra, Muhammad Jawad Hassan, Meghan S. Candee, Caleb P. Bupp, Kristen L. Park, Eric Muller, Pamela Lupo, Robert C. Pedersen, Amir M. Arain, Andrea Murphy, Krista Schatz, Weiyi Mu, Paige M. Kalika, Lautaro Plaza, Marissa A. Kellogg, Evelyn G. Lora, Robert P. Carson, Victoria Svystilnyk, Viviana Venegas, Rebecca R. Luke, Huiyuan Jiang, Tetiana Stetsenko, Milagros M. Dueñas-Roque, Joseph Trasmonte, Rebecca J. Burke, Anna C. E. Hurst, Douglas M. Smith, Lauren J. Massingham, Laura Pisani, Carrie E. Costin, Betsy Ostrander, Francis M. Filloux, Amitha L. Ananth, Ismail S. Mohamed, Alla Nechai, Jasmin M. Dao, Michael C. Fahey, Ermal Aliu, Stephen Falchek, Craig A. Press, Lauren Treat, Krista Eschbach, Angela Starks, Ryan Kammeyer, Joshua J. Bear, Mona Jacobson, Veronika Chernuha, Bailey Meibos, Kristen Wong, Matthew T. Sweney, A. Chris Espinoza, Colin B. Van Orman, Arie Weinstock, Ashutosh Kumar, Claudia Soler-Alfonso, Danielle A. Nolan, Muhammad Raza, Miguel David Rojas Carrion, Geetha Chari, Eric D. Marsh, Yael Shiloh-Malawsky, Sumit Parikh, Ernesto Gonzalez-Giraldo, Stephen Fulton, Yoshimi Sogawa, Kaitlyn Burns, Myroslava Malets, Johnny David Montiel Blanco, Christa W. Habela, Carey A. Wilson, Guillermo G. Guzmán, Mariia Pavliuk

Department of Pediatrics Faculty Papers

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes.

OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a …

The Importance Of An Early Onset Of Migraine Preventive Disease Control: A Roundtable Discussion, Christopher Gottschalk, Anirban Basu, Andrew Blumenfeld, Bradley Torphy, Michael J. Marmura, Jelena M. Pavlovic, Paula K. Dumas, Nim Lalvani, Dawn C. Buse

Department of Jefferson Headache Center papers and presentations

Background: Newly approved migraine preventive therapies have allowed for rapid control of migraine activity, offering potential to minimize the burden of migraine. This report summarizes a roundtable discussion convened to analyze evidence for early onset of prevention, ascertain its clinical relevance, and provide guidance for healthcare professionals in crafting goals and treatment expectations for patients with migraine initiating preventive therapy.

Methods: A virtual roundtable meeting of migraine clinicians, researchers, and patient advocates convened in October 2020. Participants reviewed and discussed data summarizing patient and healthcare professional perceptions of migraine prevention and evidence from the peer-reviewed and gray literature to develop …

Neurodevelopment Assessment Of Small For Gestational Age Children In A Community-Based Cohort From Pakistan, Sabahat Naz, Zahra Hoodbhoy, Ali Jaffar, Sidra Kaleem Jafri, Babar Hasan, Devyani Chowdhury, Melissa Gladstone

Department of Paediatrics and Child Health

Background: Children born small for gestational age (SGA) may experience more long-term neurodevelopmental issues than those born appropriate for gestational age (AGA). This study aimed to assess differences in the neurodevelopment of children born SGA or AGA within a periurban community in Pakistan.
Methods: This was a prospective cohort study in which study participants were followed from the pilot Doppler cohort study conducted in 2018. This pilot study aimed to develop a pregnancy risk stratification model using machine learning on fetal Dopplers. This project identified 119 newborns who were born SGA (2.4±0.4 kg) based on International Fetal and Newborn Growth …

Cannabidiol, ∆9 -Tetrahydrocannabinol, And Metabolites In Human Blood By Volumetric Absorptive Microsampling And Lc-Ms/Ms Following Controlled Administration In Epilepsy Patients, Federica Pigliasco, Sara Malaca, Alfredo Fabrizio Lo Faro, Anastasio Tini, Giuliana Cangemi, Alessia Cafaro, Sebastiano Barco, Antonella Riva, Angelica Pisati, Elisabetta Amadori, Pasquale Striano, Adriano Tagliabracci, Marilyn A. Huestis, Francesco Paolo Busardò

Institute of Emerging Health Professions Faculty Papers

Cannabidiol (CBD) exhibits anti-inflammatory, anxiolytic, antiseizure, and neuroprotective proprieties without addictive or psychotropic side effects, as opposed to Δ9-tetrahydrocannabinol (THC). While recreational cannabis contains higher THC and lower CBD concentrations, medical cannabis contains THC and CBD in different ratios, along with minor phytocannabinoids, terpenes, flavonoids and other chemicals. A volumetric absorptive microsampling (VAMS) method combined with ultra-high-performance liquid chromatography coupled with mass spectrometry in tandem for quantification of CBD, THC and their respective metabolites: cannabidiol-7-oic acid (7-COOH-CBD); 7-hydroxy-cannabidiol (7-OH-CBD); 6-alpha-hydroxy-cannabidiol (6-α-OH-CBD); and 6-beta-hydroxycannabidiol (6-β-OH-CBD); 11- Hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH). After overnight enzymatic glucuronide hydrolysis at 37°C, samples underwent acidic …

Biological Networks And Complexity In Early-Onset Motor Neuron Diseases, Matthew E. R. Butchbach, Rod C. Scott

Department of Pediatrics Faculty Papers

Motor neuron diseases (MNDs) are neuromuscular disorders where the spinal motor neurons–either the cell bodies themselves or their axons–are the primary cells affected. To date, there are 120 different genes that are lost or mutated in pediatric-onset MNDs. Most of these childhood-onset disorders, aside from spinal muscular atrophy (SMA), lack viable therapeutic options. Previous research on MNDs has focused on understanding the pathobiology of a single, specific gene mutation and targeting therapies to that pathobiology. This reductionist approach has yielded therapeutic options for a specific disorder, in this case SMA. Unfortunately, therapies specific for SMA have not been effective against …