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Articles 331 - 360 of 853

Full-Text Articles in Neurology

Tardive Dyskinesia In Older Persons Taking Antipsychotics, Leslie Citrome, Stuart H Isaacson, Danielle Larson, Daniel Kremens Oct 2021

Tardive Dyskinesia In Older Persons Taking Antipsychotics, Leslie Citrome, Stuart H Isaacson, Danielle Larson, Daniel Kremens

Department of Neurology Faculty Papers

Tardive dyskinesia (TD) is a hyperkinetic movement disorder caused by the use of dopamine receptor-blocking agents (DRBAs), a category of medications that includes first-and second-generation antipsychotics (APs) and agents such as metoclopramide that are used for the treatment of nausea and gastrointestinal dysmotility. While TD can affect people of all ages, older age is associated with increased risk of TD and also with the emergence of TD occurring after shorter treatment durations and lower dosages of DRBAs. TD is characterized by involuntary movements that include the face, limbs, and trunk, and is associated with increased comorbidities, social stigmatization, and impaired …


Dynamic Network Connectivity Reveals Markers Of Response To Deep Brain Stimulation In Parkinson’S Disease, Chengyuan Wu, Caio Matias, Thomas Foltynie, Patricia Limousin, Ludvic Zrinzo, Harith Akram Oct 2021

Dynamic Network Connectivity Reveals Markers Of Response To Deep Brain Stimulation In Parkinson’S Disease, Chengyuan Wu, Caio Matias, Thomas Foltynie, Patricia Limousin, Ludvic Zrinzo, Harith Akram

Department of Neurosurgery Faculty Papers

Background: Neuronal loss in Parkinson’s Disease (PD) leads to widespread neural network dysfunction. While graph theory allows for analysis of whole brain networks, patterns of functional connectivity (FC) associated with motor response to deep brain stimulation of the subthalamic nucleus (STN-DBS) have yet to be explored.

Objective/Hypothesis: To investigate the distributed network properties associated with STN-DBS in patients with advanced PD.

Methods: Eighteen patients underwent 3-Tesla resting state functional MRI (rs-fMRI) prior to STN-DBS. Improvement in UPDRS-III scores following STN-DBS were assessed 1 year after implantation. Independent component analysis (ICA) was applied to extract spatially independent components (ICs) from the …


Dynamic Network Connectivity Reveals Markers Of Response To Deep Brain Stimulation In Parkinson's Disease, Chengyuan Wu, Caio Matias, Thomas Foltynie, Patricia Limousin, Ludvic Zrinzo, Harith Akram Oct 2021

Dynamic Network Connectivity Reveals Markers Of Response To Deep Brain Stimulation In Parkinson's Disease, Chengyuan Wu, Caio Matias, Thomas Foltynie, Patricia Limousin, Ludvic Zrinzo, Harith Akram

Department of Neurosurgery Faculty Papers

Background: Neuronal loss in Parkinson's Disease (PD) leads to widespread neural network dysfunction. While graph theory allows for analysis of whole brain networks, patterns of functional connectivity (FC) associated with motor response to deep brain stimulation of the subthalamic nucleus (STN-DBS) have yet to be explored.

Objective/Hypothesis: To investigate the distributed network properties associated with STN-DBS in patients with advanced PD.

Methods: Eighteen patients underwent 3-Tesla resting state functional MRI (rs-fMRI) prior to STN-DBS. Improvement in UPDRS-III scores following STN-DBS were assessed 1 year after implantation. Independent component analysis (ICA) was applied to extract spatially independent components (ICs) from the …


Prognostic Implications Of Epidermal And Platelet-Derived Growth Factor Receptor Alterations In 2 Cohorts Of Idh, Iyad Alnahhas, Appaji Rayi, Maria Del Pilar Guillermo Prieto Eibl, Shirley Ong, Pierre Giglio, Vinay Puduvalli Oct 2021

Prognostic Implications Of Epidermal And Platelet-Derived Growth Factor Receptor Alterations In 2 Cohorts Of Idh, Iyad Alnahhas, Appaji Rayi, Maria Del Pilar Guillermo Prieto Eibl, Shirley Ong, Pierre Giglio, Vinay Puduvalli

Department of Neurology Faculty Papers

Background: Glioblastoma remains a deadly brain cancer with dismal prognosis. Genetic alterations, including IDH mutations, 1p19q co-deletion status and MGMT promoter methylation have been proven to be prognostic and predictive to response to treatment in gliomas. In this manuscript, we aimed to correlate other mutations and genetic alterations with various clinical endpoints in patients with IDH-wild-type (IDHwt) glioblastoma.

Methods: We compiled a comprehensive clinically annotated database of IDHwt GBM patients treated at the Ohio State University Wexner Medical Center for whom we had mutational data through a CLIA-certified genomic laboratory. We then added data that is publicly available from Memorial …


Management Of Coincident Pituitary Macroadenoma And Cavernous Carotid Aneurysm: A Systematic Literature Review., Keenan J. Piper, Michael Karsy, Blair Barton, Mindy Rabinowitz, Marc R. Rosen, Gurston G. Nyquist, James J. Evans, Stavropoula Tjoumakaris, Christopher J. Farrell Sep 2021

Management Of Coincident Pituitary Macroadenoma And Cavernous Carotid Aneurysm: A Systematic Literature Review., Keenan J. Piper, Michael Karsy, Blair Barton, Mindy Rabinowitz, Marc R. Rosen, Gurston G. Nyquist, James J. Evans, Stavropoula Tjoumakaris, Christopher J. Farrell

Department of Neurosurgery Faculty Papers

Introduction

Pituitary adenomas are a common intracranial pathology with an incidence of 15 to 20% in the population while cerebral aneurysms are less common with a prevalence of 1:50 patients. The incidence of aneurysms in patients with pituitary adenoma has been estimated at 2.3 to 5.4% of patients; however, this remains unclear. Equally, the management of concomitant lesions lacks significant understanding.

Methods

A case report is presented of a concomitant cerebral aneurysm and pituitary adenoma managed by minimally invasive endovascular and endoscopic methods, respectively. A systematic review of the literature for terms "pituitary adenoma" and "aneurysm" yielded 494 studies that …


Genetic Variation In Padi6-Padi4 On 1p36.13 Is Associated With Common Forms Of Human Generalized Epilepsy, Russell J. Buono, Jonathan P. Bradfield, Zhi Wei, Michael R. Sperling, Dennis J. Dlugos, Michael D. Privitera, Jacqueline A. French, Warren Lo, Patrick Cossette, Steven C. Schachter, Heather Basehore, Falk W. Lohoff, Struan F.A. Grant, Thomas N. Ferraro, Hakon Hakonarson Sep 2021

Genetic Variation In Padi6-Padi4 On 1p36.13 Is Associated With Common Forms Of Human Generalized Epilepsy, Russell J. Buono, Jonathan P. Bradfield, Zhi Wei, Michael R. Sperling, Dennis J. Dlugos, Michael D. Privitera, Jacqueline A. French, Warren Lo, Patrick Cossette, Steven C. Schachter, Heather Basehore, Falk W. Lohoff, Struan F.A. Grant, Thomas N. Ferraro, Hakon Hakonarson

Department of Neurology Faculty Papers

We performed a genome-wide association study (GWAS) to identify genetic variation associated with common forms of idiopathic generalized epilepsy (GE) and focal epilepsy (FE). Using a cohort of 2220 patients and 14,448 controls, we searched for single nucleotide polymorphisms (SNPs) associated with GE, FE and both forms combined. We did not find any SNPs that reached genome-wide statistical significance (p ≤ 5 × 10−8) when comparing all cases to all controls, and few SNPs of interest comparing FE cases to controls. However, we document multiple linked SNPs in the PADI6-PADI4 genes that reach genome-wide significance and are associated …


Language Tasks And The Network Control Role Of The Left Inferior Frontal Gyrus, John D Medaglia, Denise Y Harvey, Apoorva S Kelkar, Jared P Zimmerman, Joely A Mass, Danielle S Bassett, Roy H Hamilton Sep 2021

Language Tasks And The Network Control Role Of The Left Inferior Frontal Gyrus, John D Medaglia, Denise Y Harvey, Apoorva S Kelkar, Jared P Zimmerman, Joely A Mass, Danielle S Bassett, Roy H Hamilton

Department of Neurology Faculty Papers

Recent work has combined cognitive neuroscience and control theory to make predictions about cognitive control functions. Here, we test a link between whole-brain theories of semantics and the role of the left inferior frontal gyrus (LIFG) in controlled language performance using network control theory (NCT), a branch of systems engineering. Specifically, we examined whether two properties of node controllability, boundary and modal controllability, were linked to semantic selection and retrieval on sentence completion and verb generation tasks. We tested whether the controllability of the left IFG moderated language selection and retrieval costs and the effects of continuous θ burst stimulation …


Activity-Dependent Modulation Of Synapse-Regulating Genes In Astrocytes, Isabella Farhy-Tselnicker, Matthew M Boisvert, Hanqing Liu, Cari Dowling, Galina A Erikson, Elena Blanco-Suarez, Chen Farhy, Maxim N Shokhirev, Joseph R Ecker, Nicola J Allen Sep 2021

Activity-Dependent Modulation Of Synapse-Regulating Genes In Astrocytes, Isabella Farhy-Tselnicker, Matthew M Boisvert, Hanqing Liu, Cari Dowling, Galina A Erikson, Elena Blanco-Suarez, Chen Farhy, Maxim N Shokhirev, Joseph R Ecker, Nicola J Allen

Department of Neurosurgery Faculty Papers

Astrocytes regulate the formation and function of neuronal synapses via multiple signals, however, what controls regional and temporal expression of these signals during development is unknown. We determined the expression profile of astrocyte synapse-regulating genes in the developing mouse visual cortex, identifying astrocyte signals that show differential temporal and layer-enriched expression. These patterns are not intrinsic to astrocytes, but regulated by visually-evoked neuronal activity, as they are absent in mice lacking glutamate release from thalamocortical terminals. Consequently, synapses remain immature. Expression of synapse-regulating genes and synaptic development are also altered when astrocyte signaling is blunted by diminishing calcium release from …


Cross-Sectional Analysis Of Baseline Visual Parameters In Subjects Recruited Into The Rescue And Reverse Nd4-Lhon Gene Therapy Studies, Mark Moster, Robert C Sergott, Nancy J Newman, Patrick Yu-Wai-Man, Valerio Carelli, Molly Scannell Bryan, Gerard Smits, Valérie Biousse, Catherine Vignal-Clermont, Thomas Klopstock, Alfredo A Sadun, Adam A. Debusk, Michele Carbonelli, Rabih Hage, Siegfried Priglinger, Rustum Karanjia, Laure Blouin, Magali Taiel, Barrett Katz, José Alain Sahel Sep 2021

Cross-Sectional Analysis Of Baseline Visual Parameters In Subjects Recruited Into The Rescue And Reverse Nd4-Lhon Gene Therapy Studies, Mark Moster, Robert C Sergott, Nancy J Newman, Patrick Yu-Wai-Man, Valerio Carelli, Molly Scannell Bryan, Gerard Smits, Valérie Biousse, Catherine Vignal-Clermont, Thomas Klopstock, Alfredo A Sadun, Adam A. Debusk, Michele Carbonelli, Rabih Hage, Siegfried Priglinger, Rustum Karanjia, Laure Blouin, Magali Taiel, Barrett Katz, José Alain Sahel

Wills Eye Hospital Papers

OBJECTIVE: This report presents a cross-sectional analysis of the baseline characteristics of subjects with Leber hereditary optic neuropathy enrolled in the gene therapy trials RESCUE and REVERSE, to illustrate the evolution of visual parameters over the first year after vision loss.

METHODS: RESCUE and REVERSE were 2 phase III clinical trials designed to assess the efficacy of rAAV2/2-ND4 gene therapy in ND4-LHON subjects. At enrollment, subjects had vision loss for ≤6 months in RESCUE, and between 6 and 12 months in REVERSE. Functional visual parameters (best-corrected visual acuity [BCVA], contrast sensitivity [CS], and Humphrey Visual Field [HVF]) and structural parameters …


Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy For Leber Hereditary Optic Neuropathy: The Restore Study, Valérie Biousse, Nancy J Newman, Patrick Yu-Wai-Man, Valerio Carelli, Mark Moster, Catherine Vignal-Clermont, Thomas Klopstock, Alfredo A Sadun, Robert C Sergott, Rabih Hage, Simona Esposti, Chiara La Morgia, Claudia Priglinger, Rustum Karanja, Laure Blouin, Magali Taiel, José-Alain Sahel Sep 2021

Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy For Leber Hereditary Optic Neuropathy: The Restore Study, Valérie Biousse, Nancy J Newman, Patrick Yu-Wai-Man, Valerio Carelli, Mark Moster, Catherine Vignal-Clermont, Thomas Klopstock, Alfredo A Sadun, Robert C Sergott, Rabih Hage, Simona Esposti, Chiara La Morgia, Claudia Priglinger, Rustum Karanja, Laure Blouin, Magali Taiel, José-Alain Sahel

Wills Eye Hospital Papers

BACKGROUND: RESCUE and REVERSE were 2 Phase 3 clinical trials that assessed the efficacy and safety of intravitreal gene therapy with lenadogene nolparvovec (rAAV2/2-ND4) for the treatment of Leber hereditary optic neuropathy (LHON). RESTORE is the long-term follow-up study of subjects treated in the RESCUE and REVERSE trials.

METHODS: In RESCUE and REVERSE, 76 subjects with LHON because of the m.11778 G>A mutation in the mitochondrial gene ND4 received a single unilateral intravitreal injection of lenadogene nolparvovec. After 96 weeks, 61 subjects were enrolled in the long-term follow-up study RESTORE. The best-corrected visual acuity (BCVA) was assessed over a …


Theta-Burst Stimulation Entrains Frequency-Specific Oscillatory Responses., Ethan A. Solomon, Michael R. Sperling, Ashwini D. Sharan, Paul A. Wanda, Deborah F. Levy, Anastasia Lyalenko, Isaac Pedisich, Daniel S. Rizzuto, Michael J. Kahana Aug 2021

Theta-Burst Stimulation Entrains Frequency-Specific Oscillatory Responses., Ethan A. Solomon, Michael R. Sperling, Ashwini D. Sharan, Paul A. Wanda, Deborah F. Levy, Anastasia Lyalenko, Isaac Pedisich, Daniel S. Rizzuto, Michael J. Kahana

Department of Neurology Faculty Papers

BACKGROUND: Brain stimulation has emerged as a powerful tool in human neuroscience, becoming integral to next-generation psychiatric and neurologic therapeutics. Theta-burst stimulation (TBS), in which electrical pulses are delivered in rhythmic bouts of 3-8 Hz, seeks to recapitulate neural activity seen endogenously during cognitive tasks. A growing literature suggests that TBS can be used to alter or enhance cognitive processes, but little is known about how these stimulation events influence underlying neural activity.

OBJECTIVE: Our study sought to investigate the effect of direct electrical TBS on mesoscale neural activity in humans by asking (1) whether TBS evokes persistent theta oscillations …


Advances In The Diagnosis And Treatment Of Krabbe Disease, David A Wenger, Paola Luzi, Mohammad Rafi Aug 2021

Advances In The Diagnosis And Treatment Of Krabbe Disease, David A Wenger, Paola Luzi, Mohammad Rafi

Department of Neurology Faculty Papers

Krabbe disease is an autosomal recessive leukodystrophy caused by pathogenic variants in the galactocerebrosidase (GALC) gene. GALC activity is needed for the lysosomal hydrolysis of galactosylceramide, an important component of myelin. While most patients are infants, older patients are also diagnosed. Starting in 1970, a diagnosis could be made by measuring GALC activity in leukocytes and cultured cells. After the purification of GALC in 1993, the cDNA and genes were cloned. Over 260 disease-causing variants as well as activity lowering benign variants have been identified. While some pathogenic variants can be considered “severe,” others can be considered “mild.” The combination …


Analysis Of Deep Brain Stimulation Lead Targeting In The Stimulation Of Anterior Nucleus Of The Thalamus For Epilepsy Clinical Trial., Robert E. Gross, Robert S. Fisher, Michael R. Sperling, Jonathon E. Giftakis, Paul H. Stypulkowski Aug 2021

Analysis Of Deep Brain Stimulation Lead Targeting In The Stimulation Of Anterior Nucleus Of The Thalamus For Epilepsy Clinical Trial., Robert E. Gross, Robert S. Fisher, Michael R. Sperling, Jonathon E. Giftakis, Paul H. Stypulkowski

Department of Neurology Faculty Papers

BACKGROUND: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is an effective therapy for patients with drug-resistant focal epilepsy. Best practices for surgical targeting of the ANT can be refined as new information becomes available regarding effective stimulation sites.

OBJECTIVE: To conduct a retrospective analysis of the relationship between outcomes (seizure reduction during year 1) and DBS lead locations in subjects from the SANTÉ pivotal trial (Stimulation of ANT for Epilepsy) based upon recent clinical findings.

METHODS: Postoperative images from SANTÉ subjects (n = 101) were evaluated with respect to lead trajectory relative to defined anatomic …


Psychological Problems Among Patients With Chronic Medical Disorders During The Covid-19 Pandemic, Ali Akbar Asadi-Pooya, Seyed Ali Nabavizadeh, Saeid Sadeghian, Mina Shahisavandi, Zohreh Barzegar, Abdullah Nezafat, Nahid Ashjazadeh, Hamed Bazrafshan Drissi, Ali Sahraian Aug 2021

Psychological Problems Among Patients With Chronic Medical Disorders During The Covid-19 Pandemic, Ali Akbar Asadi-Pooya, Seyed Ali Nabavizadeh, Saeid Sadeghian, Mina Shahisavandi, Zohreh Barzegar, Abdullah Nezafat, Nahid Ashjazadeh, Hamed Bazrafshan Drissi, Ali Sahraian

Department of Neurology Faculty Papers

The aim of the current study was to investigate the rates of stress, anxiety, and depression among people in south Iran (a group from the general population without a history of any chronic medical problems, and cohorts of patients were recruited from epilepsy, diabetes, and cardiac disease clinics). We surveyed a sample of people during September 2020: a group of the general population without a history of any chronic medical problems, people with epilepsy, people with diabetes mellitus (DM), and people with cardiac problems. The survey included four general questions and two COVID-19 specific questions [contracting COVID-19, relatives with COVID-19]. …


Hur Plays A Positive Role To Strengthen The Signaling Pathways Of Cd4+T Cell Activation And Th17 Cell Differentiation, Shiguang Yu, Morgan Tripod, Ulus Atasoy, Jing Chen Aug 2021

Hur Plays A Positive Role To Strengthen The Signaling Pathways Of Cd4+T Cell Activation And Th17 Cell Differentiation, Shiguang Yu, Morgan Tripod, Ulus Atasoy, Jing Chen

Department of Neurology Faculty Papers

After antigen and/or different cytokine stimulation, CD4+ T cells activated and differentiated into distinct T helper (Th) cells via differential T cell signaling pathways. Transcriptional regulation of the activation and differentiation of naïve CD4+ T cells into distinct lineage Th cells such as Th17 cells has been fully studied. However, the role of RNA-binding protein HuR in the signaling pathways of their activation and differentiation has not been well characterized. Here, we used HuR conditional knockout (HuR KO) CD4+ T cells to study mechanisms underlying HuR regulation of T cell activation and differentiation through distinct signaling pathways. …


Pathophysiology Of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: A Review., William S. Dodd, Dimitri Laurent, Aaron S. Dumont, David M. Hasan, Pascal M. Jabbour, Robert M. Starke, Koji Hosaka, Adam J. Polifka, Brian L. Hoh, Nohra Chalouhi Aug 2021

Pathophysiology Of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: A Review., William S. Dodd, Dimitri Laurent, Aaron S. Dumont, David M. Hasan, Pascal M. Jabbour, Robert M. Starke, Koji Hosaka, Adam J. Polifka, Brian L. Hoh, Nohra Chalouhi

Department of Neurosurgery Faculty Papers

Delayed cerebral ischemia is a major predictor of poor outcomes in patients who suffer subarachnoid hemorrhage. Treatment options are limited and often ineffective despite many years of investigation and clinical trials. Modern advances in basic science have produced a much more complex, multifactorial framework in which delayed cerebral ischemia is better understood and novel treatments can be developed. Leveraging this knowledge to improve outcomes, however, depends on a holistic understanding of the disease process. We conducted a review of the literature to analyze the current state of investigation into delayed cerebral ischemia with emphasis on the major themes that have …


A Phase 1b/2a Study Of Soticlestat As Adjunctive Therapy In Participants With Developmental And/Or Epileptic Encephalopathies., Jonathan J. Halford, Michael R. Sperling, Dimitrios Arkilo, Mahnaz Asgharnejad, Celia Zinger, Rengyi Xu, Matthew During, Jacqueline A. French Aug 2021

A Phase 1b/2a Study Of Soticlestat As Adjunctive Therapy In Participants With Developmental And/Or Epileptic Encephalopathies., Jonathan J. Halford, Michael R. Sperling, Dimitrios Arkilo, Mahnaz Asgharnejad, Celia Zinger, Rengyi Xu, Matthew During, Jacqueline A. French

Department of Neurology Faculty Papers

OBJECTIVE: To evaluate the safety, tolerability, and pharmacokinetics of soticlestat, a first-in-class cholesterol 24-hydroxylase inhibitor, in adults with developmental and/or epileptic encephalopathies (DEE).

METHODS: The study comprised a 30-day, randomized, double-blind, placebo-controlled phase (Part A), followed by a 55-day open-label phase (Part B) (ClinicalTrials.gov ID: NCT03166215) . In Part A, patients with DEE and at least one bilateral motor seizure during the 4-week prospective baseline period were randomized 4:1 to receive soticlestat or placebo, in addition to their usual antiseizure medication. In Part B, all patients received open-label soticlestat. Soticlestat doses were titrated according to tolerability to a maximum of …


Distinct Cortical Systems Reinstate The Content And Context Of Episodic Memories., James E. Kragel, Youssef Ezzyat, Bradley C. Lega, Michael R. Sperling, Gregory A. Worrell, Robert E. Gross, Barbara C. Jobst, Sameer A. Sheth, Kareem A. Zaghloul, Joel M. Stein, Michael J. Kahana Jul 2021

Distinct Cortical Systems Reinstate The Content And Context Of Episodic Memories., James E. Kragel, Youssef Ezzyat, Bradley C. Lega, Michael R. Sperling, Gregory A. Worrell, Robert E. Gross, Barbara C. Jobst, Sameer A. Sheth, Kareem A. Zaghloul, Joel M. Stein, Michael J. Kahana

Department of Neurology Faculty Papers

Episodic recall depends upon the reinstatement of cortical activity present during the formation of a memory. Evidence from functional neuroimaging and invasive recordings in humans suggest that reinstatement organizes our memories by time or content, yet the neural systems involved in reinstating these unique types of information remain unclear. Here, combining computational modeling and intracranial recordings from 69 epilepsy patients, we show that two cortical systems uniquely reinstate the semantic content and temporal context of previously studied items during free recall. Examining either the posterior medial or anterior temporal networks, we find that forward encoding models trained on the brain's …


Erratum To: Characterizing Benefit From Temozolomide In Mgmt Promoter Unmethylated And Methylated Glioblastoma: A Systematic Review And Meta-Analysis, Iyad Alnahhas, Mouaz Alsawas, Appaji Rayi, Joshua D Palmer, Raju Raval, Shirley Ong, Pierre Giglio, Mohammad Hassan Murad, Vinay Puduvalli Jul 2021

Erratum To: Characterizing Benefit From Temozolomide In Mgmt Promoter Unmethylated And Methylated Glioblastoma: A Systematic Review And Meta-Analysis, Iyad Alnahhas, Mouaz Alsawas, Appaji Rayi, Joshua D Palmer, Raju Raval, Shirley Ong, Pierre Giglio, Mohammad Hassan Murad, Vinay Puduvalli

Department of Neurology Faculty Papers

[This corrects the article DOI: 10.1093/noajnl/vdaa082.].


Rapidly Progressive Acth-Dependent Cushing’S Disease Masquerading As Ectopic Acth-Producing Cushing’S Syndrome: Illustrative Case, Siyuan Yu, Michael Karsy, Jeffery Miller, Stephanie R. Beldick, Mark T. Curtis, Marc Rosen, James J. Evans Jul 2021

Rapidly Progressive Acth-Dependent Cushing’S Disease Masquerading As Ectopic Acth-Producing Cushing’S Syndrome: Illustrative Case, Siyuan Yu, Michael Karsy, Jeffery Miller, Stephanie R. Beldick, Mark T. Curtis, Marc Rosen, James J. Evans

Department of Neurosurgery Faculty Papers

BACKGROUND Cushing’s disease (CD) remains a challenging condition to diagnose and treat. This case study highlights the challenges of diagnosing CDwhen faced with discrepant clinical, biochemical, and radiologicalfindings.

OBSERVATIONS A 62-year-old man presented with rapid evolution of symptoms, including depression, fatigue, and extreme muscle atrophy, whichresulted in the patient being a wheelchair user over the course of a few months. His rapid clinical course in conjunction with hypercortisolemia in thesetting of a pituitary macroadenoma involving the cavernous sinus, two large pulmonary nodules, and urine-free cortisol levels in the thousandssuggested an aggressive ectopic adrenocorticotropic hormone (ACTH) source. After extensive testing ruled …


An Educational Workshop To Improve Neurology Resident Understanding Of Burnout, Substance Abuse, And Mood Disorders., Ryan Donaghy, Shiori Tomatsu, Patrick Kerns, Courtney White, Jeffrey Ratliff Jul 2021

An Educational Workshop To Improve Neurology Resident Understanding Of Burnout, Substance Abuse, And Mood Disorders., Ryan Donaghy, Shiori Tomatsu, Patrick Kerns, Courtney White, Jeffrey Ratliff

Department of Neurology Faculty Papers

Introduction: Burnout, substance abuse, and mood disorders are prevalent among neurology residents. Increased recognition of concerning behaviors might encourage more access to mental health resources and reduce burnout.

Methods: We created an educational resource reviewing burnout, substance abuse, and mood disorders for neurology residents. This resource included an online module (control) and a role-play scenario offered only to one cohort (intervention). Online surveys assessed knowledge as well as confidence in the ability to recognize concerning behaviors. A practical assessment using a previously published "Stressed Resident" video was also conducted among resident cohorts.

Results: Of neurology residents, 18 participated in the …


A Machine Learning Approach To First Pass Reperfusion In Mechanical Thrombectomy: Prediction And Feature Analysis., Lohit Velagapudi, Nikolaos Mouchtouris, Richard F Schmidt, David Vuong, Omaditya Khanna, Ahmad Sweid, Bryan Sadler, Fadi Al-Saiegh, M Reid Gooch, Pascal Jabbour, Robert H Rosenwasser, Stavropoula Tjoumakaris Jul 2021

A Machine Learning Approach To First Pass Reperfusion In Mechanical Thrombectomy: Prediction And Feature Analysis., Lohit Velagapudi, Nikolaos Mouchtouris, Richard F Schmidt, David Vuong, Omaditya Khanna, Ahmad Sweid, Bryan Sadler, Fadi Al-Saiegh, M Reid Gooch, Pascal Jabbour, Robert H Rosenwasser, Stavropoula Tjoumakaris

Department of Neurosurgery Faculty Papers

INTRODUCTION: Novel machine learning (ML) methods are being investigated across medicine for their predictive capabilities while boasting increased adaptability and generalizability. In our study, we compare logistic regression with machine learning for feature importance analysis and prediction in first-pass reperfusion.

METHODS: We retrospectively identified cases of ischemic stroke treated with mechanical thrombectomy (MT) at our institution from 2012-2018. Significant variables used in predictive modeling were demographic characteristics, medical history, admission NIHSS, and stroke characteristics. Outcome was binarized TICI on first pass (0-2a vs 2b-3). Shapley feature importance plots were used to identify variables that strongly affected outcomes.

RESULTS: Accuracy for …


Discrepancies In Stroke Distribution And Dataset Origin In Machine Learning For Stroke., Lohit Velagapudi, Nikolaos Mouchtouris, Michael P Baldassari, David Nauheim, Omaditya Khanna, Fadi Al Saiegh, Nabeel Herial, M Reid Gooch, Stavropoula Tjoumakaris, Robert H Rosenwasser, Pascal Jabbour Jul 2021

Discrepancies In Stroke Distribution And Dataset Origin In Machine Learning For Stroke., Lohit Velagapudi, Nikolaos Mouchtouris, Michael P Baldassari, David Nauheim, Omaditya Khanna, Fadi Al Saiegh, Nabeel Herial, M Reid Gooch, Stavropoula Tjoumakaris, Robert H Rosenwasser, Pascal Jabbour

Department of Neurosurgery Faculty Papers

BACKGROUND: Machine learning algorithms depend on accurate and representative datasets for training in order to become valuable clinical tools that are widely generalizable to a varied population. We aim to conduct a review of machine learning uses in stroke literature to assess the geographic distribution of datasets and patient cohorts used to train these models and compare them to stroke distribution to evaluate for disparities.

AIMS: 582 studies were identified on initial searching of the PubMed database. Of these studies, 106 full texts were assessed after title and abstract screening which resulted in 489 papers excluded. Of these 106 studies, …


The Development Of Lived Experience-Centered Word Clouds To Support Research Uncertainty Gathering In Degenerative Cervical Myelopathy: Results From An Engagement Process And Protocol For Their Evaluation, Via A Nested Randomized Controlled Trial, Benjamin M Davies, Oliver D Mowforth, Danyal Z Khan, Xiaoyu Yang, Sybil R L Stacpoole, Olesja Hazenbiller, Toto Gronlund, Lindsay Tetreault, Sukhvinder Kalsi-Ryan, Michelle L Starkey, Iwan Sadler, Ellen Sarewitz, Delphine Houlton, Julia Carter, Evangeline Howard, Vafa Rahimi-Movaghar, James D Guest, Bizhan Aarabi, Brian K Kwon, Shekar N Kurpad, James Harrop, Jefferson R Wilson, Robert Grossman, Emma K Smith, Angus G K Mcnair, Michael G Fehlings, Mark R N Kotter Jun 2021

The Development Of Lived Experience-Centered Word Clouds To Support Research Uncertainty Gathering In Degenerative Cervical Myelopathy: Results From An Engagement Process And Protocol For Their Evaluation, Via A Nested Randomized Controlled Trial, Benjamin M Davies, Oliver D Mowforth, Danyal Z Khan, Xiaoyu Yang, Sybil R L Stacpoole, Olesja Hazenbiller, Toto Gronlund, Lindsay Tetreault, Sukhvinder Kalsi-Ryan, Michelle L Starkey, Iwan Sadler, Ellen Sarewitz, Delphine Houlton, Julia Carter, Evangeline Howard, Vafa Rahimi-Movaghar, James D Guest, Bizhan Aarabi, Brian K Kwon, Shekar N Kurpad, James Harrop, Jefferson R Wilson, Robert Grossman, Emma K Smith, Angus G K Mcnair, Michael G Fehlings, Mark R N Kotter

Department of Neurosurgery Faculty Papers

OBJECTIVES: AO Spine REsearch objectives and Common Data Elements for Degenerative Cervical Myelopathy [RECODE-DCM] is a multi-stakeholder consensus process aiming to promote research efficiency in DCM. It aims to establish the top 10 research uncertainties, through a James Lind Alliance Priority Setting Partnership [PSP]. Through a consensus process, research questions are generated and ranked. The inclusion of people with cervical myelopathy [PwCM] is central to the process. We hypothesized that presenting PwCM experience through word cloud generation would stimulate other key stakeholders to generate research questions better aligned with PwCM needs. This protocol outlines our plans to evaluate this as …


Long-Term Efficacy And Tolerability Of Adjunctive Brivaracetam In Adults With Focal To Bilateral Tonic-Clonic (Secondary Generalized) Seizures: Post Hoc Pooled Analysis, Brian D Moseley, Svetlana Dimova, Sami Elmoufti, Cédric Laloyaux, Aliakbar Asadi-Pooya Jun 2021

Long-Term Efficacy And Tolerability Of Adjunctive Brivaracetam In Adults With Focal To Bilateral Tonic-Clonic (Secondary Generalized) Seizures: Post Hoc Pooled Analysis, Brian D Moseley, Svetlana Dimova, Sami Elmoufti, Cédric Laloyaux, Aliakbar Asadi-Pooya

Department of Neurology Faculty Papers

This post hoc analysis was conducted to evaluate the efficacy, tolerability, and health-related quality of life during long-term adjunctive brivaracetam (BRV) treatment in adult patients with focal to bilateral tonic-clonic seizures (FBTCS). Patients (≥ 16 years) were included in this post hoc analysis if they were randomized to BRV or placebo in double-blind, placebo-controlled (N01252 [NCT00490035], N01253 [NCT00464269], N01358 [NCT01261325]; core) trials, and received adjunctive BRV in the corresponding long-term follow-up (N01125 [NCT00175916], N01199 [NCT00150800], N01379 [NCT01339559]) trials, and reported FBTCS during the 8-week prospective baseline (core trial). Efficacy (concomitant levetiracetam excluded) and tolerability (concomitant levetiracetam included) were assessed from …


Outcomes Of Rescue Endovascular Treatment Of Emergent Large Vessel Occlusion In Patients With Underlying Intracranial Atherosclerosis: Insights From Star., Sami Al Kasab, Eyad Almallouhi, Ali Alawieh, Stacey Wolfe, Kyle M. Fargen, Adam S. Arthur, Nitin Goyal, Travis Dumont, Peter Kan, Joon-Tae Kim, Reade De Leacy, Ilko Maier, Joshua Osbun, Ansaar Rai, Pascal Jabbour, Jonathan A. Grossberg, Min S. Park, Robert M. Starke, Roberto Crosa, Alejandro M. Spiotta Jun 2021

Outcomes Of Rescue Endovascular Treatment Of Emergent Large Vessel Occlusion In Patients With Underlying Intracranial Atherosclerosis: Insights From Star., Sami Al Kasab, Eyad Almallouhi, Ali Alawieh, Stacey Wolfe, Kyle M. Fargen, Adam S. Arthur, Nitin Goyal, Travis Dumont, Peter Kan, Joon-Tae Kim, Reade De Leacy, Ilko Maier, Joshua Osbun, Ansaar Rai, Pascal Jabbour, Jonathan A. Grossberg, Min S. Park, Robert M. Starke, Roberto Crosa, Alejandro M. Spiotta

Department of Neurosurgery Faculty Papers

Background: Some emergent large vessel occlusions (ELVOs) are refractory to reperfusion because of underlying intracranial atherosclerosis (ICAS), often requiring rescue therapy (RT) with balloon angioplasty, stenting, or both. In this study, we investigate the safety, efficacy, and long-term outcomes of RT in the setting of mechanical thrombectomy for ICAS-related ELVO.

Methods and Results: We queried the databases of 10 thrombectomy‐capable centers in North America and Europe included in STAR (Stroke Thrombectomy and Aneurysm Registry). Patients with ELVO who underwent ICAS‐related RT were included. A matched sample was produced for variables of age, admission National Institute of Health Stroke …


Are Guidelines Important? Results Of A Prospective Quality Improvement Lumbar Fusion Project., James Harrop, Alexandra Emes, Ameet Chitale, Chengyuan Wu, Fadi Al-Saiegh, Geoffrey Stricsek, Glenn A. Gonzalez, Jack Jallo, Joshua Heller, Kevin Hines, Lucas Philipp, Sara Thalheimer, Srinivas K. Prasad, Thiago Montenegro, Umma Fatema, Ashwini Sharan Jun 2021

Are Guidelines Important? Results Of A Prospective Quality Improvement Lumbar Fusion Project., James Harrop, Alexandra Emes, Ameet Chitale, Chengyuan Wu, Fadi Al-Saiegh, Geoffrey Stricsek, Glenn A. Gonzalez, Jack Jallo, Joshua Heller, Kevin Hines, Lucas Philipp, Sara Thalheimer, Srinivas K. Prasad, Thiago Montenegro, Umma Fatema, Ashwini Sharan

Department of Neurosurgery Faculty Papers

BACKGROUND: United States (U.S.) healthcare is a volume-based inefficient delivery system. Value requires the consideration of quality, which is lacking in most healthcare disciplines.

OBJECTIVE: To assess whether patients who met specific evidence-based medicine (EBM)-based criteria preoperatively for lumbar fusion would achieve higher rates of achieving the minimal clinical important difference (MCID) than those who did not meet the EBM indications.

METHODS: All elective lumbar fusion cases, March 2018 to August 2019, were prospectively evaluated and categorized based on EBM guidelines for surgical indications. The MCID was defined as a reduction of ≥5 points in Oswestry Disability Index (ODI). Multiple …


Are Lumbar Fusion Guidelines Followed? A Survey Of North American Spine Surgeons, Thiago Montenegro, Christopher Elia, Kevin Hines, Zorica Buser, Jefferson Wilson, Zoher Ghogawala, Shekar N Kurpad, Daniel M Sciubba, James Harrop Jun 2021

Are Lumbar Fusion Guidelines Followed? A Survey Of North American Spine Surgeons, Thiago Montenegro, Christopher Elia, Kevin Hines, Zorica Buser, Jefferson Wilson, Zoher Ghogawala, Shekar N Kurpad, Daniel M Sciubba, James Harrop

Department of Neurosurgery Faculty Papers

OBJECTIVE: To evaluate the use of guidelines for lumbar spine fusions among spine surgeons in North America.

METHODS: An anonymous survey was electronically sent to all AO Spine North America members. Survey respondents were asked to indicate their opinion surrounding the suitability of instrumented fusion in a variety of clinical scenarios. Fusion indications in accordance with North America Spine Society (NASS) guidelines for lumbar fusion were considered NASS-concordant answers. Respondents were considered to have a NASS-concordant approach if ≥ 70% (13 of 18) of their answers were NASS-concordant answers. Comparisons were performed using bivariable statistics.

RESULTS: A total of 105 …


Evaluation Of Diazepam Nasal Spray In Patients With Epilepsy Concomitantly Using Maintenance Benzodiazepines: An Interim Subgroup Analysis From A Phase 3, Long-Term, Open-Label Safety Study., Eric B Segal, Daniel Tarquinio, Ian Miller, James W Wheless, Dennis Dlugos, Victor Biton, Gregory D Cascino, Jay Desai, R Edward Hogan, Kore Liow, Michael R Sperling, Blanca Vazquez, David F Cook, Adrian L Rabinowicz, Enrique Carrazana Jun 2021

Evaluation Of Diazepam Nasal Spray In Patients With Epilepsy Concomitantly Using Maintenance Benzodiazepines: An Interim Subgroup Analysis From A Phase 3, Long-Term, Open-Label Safety Study., Eric B Segal, Daniel Tarquinio, Ian Miller, James W Wheless, Dennis Dlugos, Victor Biton, Gregory D Cascino, Jay Desai, R Edward Hogan, Kore Liow, Michael R Sperling, Blanca Vazquez, David F Cook, Adrian L Rabinowicz, Enrique Carrazana

Department of Neurology Faculty Papers

OBJECTIVE: Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness.

METHODS: A long-term, phase 3, open-label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen.

RESULTS: Among 175 patients enrolled by October 31, 2019, …


Aggressive Herpes Zoster In Young Patients With Multiple Sclerosis Under Dimethyl Fumarate: Significance Of Cd8, Maria Anagnostouli, Georgios Velonakis, Marinos Dalakas May 2021

Aggressive Herpes Zoster In Young Patients With Multiple Sclerosis Under Dimethyl Fumarate: Significance Of Cd8, Maria Anagnostouli, Georgios Velonakis, Marinos Dalakas

Department of Neurology Faculty Papers

Dimethyl fumarate (DMF), approved for relapsing-remitting multiple sclerosis (RRMS), exerts immune-mediated mechanisms crucial for T-cell survival and migration, preferentially reducing CD8+ T cells.1 Although baseline absolute lymphocyte count (ALC) is considered the most critical predictor of developing lymphopenia,2 it was recently concluded that lymphocyte subset monitoring is not required for safety vigilance because T-cell subset reduction does not increase risks for serious infections.3 We present 2 young patients with RRMS, under DMF treatment, negative for HIV and SARSCoV-2 (by RT-PCR in nasal swab) and with normal follow-up white blood cell (WBC)/ALC counts, who developed severe herpes zoster (HZ) infection with …