Neurology Commons^™

Association Of Human Leukocyte Antigen Alleles With Carbamazepine-Or Lamotrigine-Induced Stevens-Johnson Syndrome And Toxic Epidermal Necrolysis In An Iranian Population: A Case-Control Study, Ladan Dastgheib, Farima Rostami, Behrouz Gharesi-Fard, Ali Akbar Asadi-Pooya, Saba Namjoo, Foroozan Tahmasebi, Maryam Hadibarhaghtalab

Department of Neurology Faculty Papers

Background: Genetic diversity in human leukocyte antigen (HLA) alleles across populations is a significant risk factor for drug-induced severe cutaneous adverse reactions (SCARs), e.g., carbamazepine (CBZ)- and lamotrigine (LTG)-induced StevensJohnson syndrome (SJS), and toxic epidermal necrolysis (TEN). The present study aimed to investigate the frequency of different HLA alleles in Iranian patients with CBZ- and LTG-induced SJS/TEN.

Methods:A case-control study was conducted from 2011 to 2018 at various hospitals affiliated with Shiraz University of Medical Sciences (Shiraz, Iran). A total of 31 patients receiving anticonvulsant drugs (CZB or LTG) were recruited and divided into two groups. The drug-induced group …

Safety And Tolerability Results Of Atogepant For The Preventive Treatment Of Episodic Migraine From A 40-Week, Open-Label Multicenter Extension Of The Phase 3 Advance Trial, Brad C Klein, Rosa Miceli, Lawrence Severt, Peter Mcallister, Laszlo Mechtler, Jennifer Mcvige, Merle Diamond, Michael J. Marmura, Hua Guo, Michelle Finnegan, Joel M Trugman

Department of Neurology Faculty Papers

Background: Atogepant is a United States Food and Drug Administration-approved oral calcitonin gene-related peptide receptor antagonist for the preventive treatment of episodic migraine. The study objective was to evaluate the long-term safety and tolerability of atogepant in participants who completed the phase 3 ADVANCE trial (NCT03777059).

Methods: This 40-week, open-label extension trial (NCT03939312) monitored safety in participants receiving oral atogepant 60 mg once daily, followed by a four-week safety follow-up period.

Results: Of the 685 participants taking at least one dose of atogepant, the treatment period was completed by 74.6% of participants with a mean (standard …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Gastric Perforation From A Migrating Ventriculoperitoneal Shunt: A Case Report And Review Of Literature, Alessio Scarascia, Elias Atallah, Maria De Abreu Pineda, Robert H. Rosenwasswer, Kevin Judy

Department of Neurosurgery Faculty Papers

Ventriculoperitoneal (VP) shunts represent a surgical option for patients affected by increased intracranial hypertension when medical management fails or is contraindicated. Complications following implantation include shunt obstruction, infection, over and under drainage, migration or disconnection of the tube, formation of a pseudocyst, and allergy to the silicone tube. We report the case of a 31-year-old woman who presented to the emergency room with nausea and generalized malaise, found to have the distal segment of the VP catheter perforating her gastric wall into the stomach lumen which required surgical intervention. In this report, we describe a rare complication associated with the …

Outcomes Of Children With Low-Grade Gliomas In Low- And Middle-Income Countries: A Systematic Review, Richard Ward, Hannah M Jones, Davis Witt, Frederick Boop, Eric Bouffet, Carlos Rodriguez-Galindo, Ibrahim Qaddoumi, Daniel C Moreira

Department of Medical Oncology Faculty Papers

Purpose: Pediatric CNS tumors are increasingly a priority, particularly with the WHO designation of low-grade glioma (LGG) as one of six index childhood cancers. There are currently limited data on outcomes of pediatric patients with LGGs in low- and middle-income countries (LMICs).

Methods: To better understand the outcomes of LGGs in LMICs, this systematic review interrogated nine literature databases.

Results: The search identified 14,977 publications. Sixteen studies from 19 countries met the selection criteria and were included for data abstraction and analysis. Eleven studies (69%) were retrospective reviews from single institutions, and one (6%) captured institutional data prospectively. The studies …

Hypoglossal Nerve Injury With C1 Lateral Mass Screw Placement: A Case Report And Review Of The Literature, Maria De Abreu Pineda, Elias Atallah, John Wainwright, Joseph Schaefer, Aria Mahtabfar, James S Harrop, Srinivas Prasad, Joshua Pelta-Heller, Ashwini Sharan, Ahilan Sivaganesan, Jack Jallo

Department of Neurosurgery Faculty Papers

We report the case of a 62-year-old man who presented with a progressive myelopathy secondary to spinal cord compression from an odontoid process fracture and subaxial central canal stenosis. The patient underwent a C1-T2 posterior decompression and instrumented fusion (PCDF) and did well immediately postoperatively. However, on POD1, he developed a right hypoglossal nerve (HN) palsy attributed to direct mechanical compression or injury from the C1 lateral mass screw (LMS), which improved following a revision and screw replacement. While HN injury is a known complication of high anterior and anterolateral cervical spine approaches as well as transcondylar screw fixation, this …

Case Report: The Promising Application Of Dynamic Functional Connectivity Analysis On An Individual With Failed Back Surgery Syndrome, Jingya Miao, Isaiah Ailes, Laura Krisa, Kristen Fleming, Devon Middleton, Kiran Talekar, Peter Natale, Feroze B. Mohamed, Kevin Hines, Caio M. Matias, Mahdi Alizadeh

Department of Neurosurgery Faculty Papers

Failed back surgery syndrome (FBSS), a chronic neuropathic pain condition, is a common indication for spinal cord stimulation (SCS). However, the mechanisms of SCS, especially its effects on supraspinal/brain functional connectivity, are still not fully understood. Resting state functional magnetic resonance imaging (rsfMRI) studies have shown characteristics in patients with chronic low back pain (cLBP). In this case study, we performed rsfMRI scanning (3.0 T) on an FBSS patient, who presented with chronic low back and leg pain following her previous lumbar microdiscectomy and had undergone permanent SCS. Appropriate MRI safety measures were undertaken to scan this subject. Seed-based functional …

Bridging Thrombolysis In Atrial Fibrillation Stroke Is Associated With Increased Hemorrhagic Complications Without Improved Outcomes, Feras Akbik, Ali Alawieh, Laurie Dimisko, Brian M. Howard, C Michael Cawley, Frank C. Tong, Fadi Nahab, Owen B. Samuels, Ilko Maier, Wuwei Feng, Nitin Goyal, Robert M. Starke, Ansaar Rai, Kyle M. Fargen, Marios N. Psychogios, Pascal Jabbour, Reade De Leacy, Saleh G. Keyrouz, Travis M. Dumont, Peter Kan, Jan Liman, Adam S. Arthur, Stacey Q. Wolfe, J. Mocco, Roberto Javier Crosa, W Christopher Fox, Benjamin Gory, Alejandro M. Spiotta, Jonathan A. Grossberg

Department of Neurosurgery Faculty Papers

BACKGROUND: Atrial fibrillation (AF) associated ischemic stroke is associated with worse functional outcomes, less effective recanalization, and increased rates of hemorrhagic complications after intravenous thrombolysis (IVT). Conversely, AF is not associated with hemorrhagic complications or functional outcomes in patients undergoing mechanical thrombectomy (MT). This differential effect of MT and IVT in AF associated stroke raises the question of whether bridging thrombolysis increases hemorrhagic complications in AF patients undergoing MT.

METHODS: This international cohort study of 22 comprehensive stroke centers analyzed patients with large vessel occlusion (LVO) undergoing MT between June 1, 2015 and December 31, 2020. Patients were divided into …

Long-Term Effectiveness Of Ivig Maintenance Therapy In 36 Patients With Gad Antibody-Positive Stiff-Person Syndrome., Jessica Yi, Marinos Dalakas

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: IVIg has been the preferred immunotherapy in stiff-person syndrome (SPS) based on a 3-month controlled trial, but whether it is also effective in inducing long-term benefits or arresting disease progression is unknown. The information is needed because SPS is a progressively disabling disease and IVIg is liberally used as chronic therapy without efficacy data. The present study explores the long-term effects of IVIg in the largest cohort of well-characterized patients with SPS followed by the same clinicians over 10 years.

METHODS: Data of 36 patients (32 glutamic acid decarboxylase [GAD] positive), diagnosed and treated with monthly maintenance …

Future Opportunities For Research In Rescue Treatments, James W. Wheless, Daniel Friedman, Gregory L. Krauss, Vikram R. Rao, Michael R Sperling, Enrique Carrazana, Adrian L. Rabinowicz

Department of Neurology Faculty Papers

Clinical studies of rescue medications for seizure clusters are limited and are designed to satisfy regulatory requirements, which may not fully consider the needs of the diverse patient population that experiences seizure clusters or utilize rescue medication. The purpose of this narrative review is to examine the factors that contribute to, or may influence the quality of, seizure cluster research with a goal of improving clinical practice. We address five areas of unmet needs and provide advice for how they could enhance future trials of seizure cluster treatments. The topics addressed in this article are: (1) unaddressed end points to …

The Impact Of Intraoperative Image-Guidance Modalities And Neurophysiologic Monitoring In The Safety Of Sacroiliac Fusions., Thiago Montenegro, Christian Hoelscher, Md, Kevin Hines, Md, Sara Thalheimer, Caio Matias, Bryan Wilent, James Harrop, Joshua E. Heller

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Retrospective observational cohort.

OBJECTIVE: A review of efficiency and safety of fluoroscopy and stereotactic navigation system for minimally invasive (MIS) Sacroiliac (SI) fusion through a lateral technique.

METHODS: Retrospective analysis of an observational cohort of 96 patients greater than 18 years old, that underwent MIS SI fusion guided by fluoroscopy or navigation between January 2013 and April 2020 with a minimum of 3 months follow-up. Intraoperative neuromonitoring (IONM) with a variable combination of electromyography (EMG), somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) was also utilized.

RESULTS: The overall complication rate in the study was 9.4%, and …

Effect Of The Covid-19 Pandemic On Seizure Control Status In Patients With Epilepsy, A A Asadi-Pooya, Seyed Ali Nabavizadeh, Mohsen Farazdaghi

Department of Neurology Faculty Papers

Background: Previous studies have shown that patients with epilepsy (PWE) perceived significant disruption in the quality and provision of care due to the coronavirus disease 2019 (COVID-19) pandemic. The present study aimed to investigate the effect of this pandemic on seizure control status and changes in seizure frequency in PWE.

Methods:A consecutive sample of adult PWE registered in the database of Shiraz Epilepsy Center (Shiraz, Iran) was included in the study. In July 2021, phone interviews were conducted with all selected patients. Information such as age, sex, last seizure, seizure type, and frequency during the 12 months before the …