Neurology Commons^™

Endovascular Thrombectomy Versus Medical Management In Isolated M2 Occlusions: Pooled Patient-Level Analysis From The Extend-Ia Trials, Inspire And Select Studies, Amrou Sarraj, Mark Parsons, Andrew Bivard, Ameer E. Hassan, Michael G. Abraham, Teddy Wu, Timothy Kleinig, Longting Lin, Chushuang (Amy) Chen, Christopher Levi

School of Medicine Publications

Objective: To evaluate functional and safety outcomes of Endovascular thrombectomy(EVT) vs Medical Management(MM) in patients with M2 occlusion and examine their association with perfusion imaging mismatch and stroke severity.

Methods: In a pooled, patient-level analysis of 3 randomized controlled trials(EXTEND-IA, EXTEND-IA-TNK part 1&2) and 2 prospective non-randomized studies(INSPIRE&SELECT), we evaluated EVT association with 90-day functional independence(mRS 0-2) in isolated M2 occlusions as compared to medical management overall and in subgroups by mismatch profile status and stroke severity.

Results: We included 517 patients(EVT=195, MM=322), baseline median(IQR) NIHSS was 13(8-19) in EVT vs 10(6-15) in MM, p

Interpretation: In patients with M2 …

Response Of Astrocyte Subpopulations Following Spinal Cord Injury., R Vivian Allahyari, Nicolette M Heinsinger, Daniel Hwang, David A Jaffe, Javad Rasouli, Stephanie Shiers, Samantha J Thomas, Theodore J Price, Abdolmohamad Rostami, Angelo C Lepore

Farber Institute for Neuroscience Faculty Papers

There is growing appreciation for astrocyte heterogeneity both across and within central nervous system (CNS) regions, as well as between intact and diseased states. Recent work identified multiple astrocyte subpopulations in mature brain. Interestingly, one subpopulation (Population C) was shown to possess significantly enhanced synaptogenic properties in vitro, as compared with other astrocyte subpopulations of adult cortex and spinal cord. Following spinal cord injury (SCI), damaged neurons lose synaptic connections with neuronal partners, resulting in persistent functional loss. We determined whether SCI induces an enhanced synaptomodulatory astrocyte phenotype by shifting toward a greater proportion of Population C cells and/or increasing …

Challenges And Opportunities For Immunotherapeutic Intervention Against Myeloid Immunosuppression In Glioblastoma, Mark A Exley, Samantha Garcia, Amelia Zellander, Jenny Zilberberg, David W. Andrews

Department of Neurosurgery Faculty Papers

Glioblastoma multiforme (GBM), the most common and deadly brain cancer, exemplifies the paradigm that cancers grow with help from an immunosuppressive tumor microenvironment (TME). In general, TME includes a large contribution from various myeloid lineage-derived cell types, including (in the brain) altered pathogenic microglia as well as monocyte-macrophages (Macs), myeloid-derived suppressor cells (MDSC) and dendritic cell (DC) populations. Each can have protective roles, but has, by definition, been coopted by the tumor in patients with progressive disease. However, evidence demonstrates that myeloid immunosuppressive activities can be reversed in different ways, leading to enthusiasm for this therapeutic approach, both alone and …

Blood–Brain Barrier Disruption Mediated By Ffa1 Receptor—Evidence Using Miniscope, Kristen L Lindenau, Jeffrey L Barr, Christopher R Higgins, Kevin T Sporici, Eugen Brailoiu, Gabriela C Brailoiu

Faculty, Staff and Student Publications

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), obtained from diet and dietary supplements, have been tested in clinical trials for the prevention or treatment of several diseases. n-3 PUFAs exert their effects by activation of free fatty acid (FFA) receptors. FFA1 receptor, expressed in the pancreas and brain, is activated by medium- to long-chain fatty acids. Despite some beneficial effects on cognition, the effects of n-3 PUFAs on the blood-brain barrier (BBB) are not clearly understood. We examined the effects of FFA1 activation on BBB permeability in vitro, using rat brain microvascular endothelial cells (RBMVEC), and in vivo, by assessing Evans …

Seizure Prediction In Epilepsy Patients, Gary Dean Cravens

NSU REACH and IPE Day

Purpose/Objective: Characterize rigorously the preictal period in epilepsy patients to improve the development of seizure prediction techniques. Background/Rationale: 30% of epilepsy patients are not well-controlled on medications and would benefit immensely from reliable seizure prediction. Methods/Methodology: Computational model consisting of in-silico Hodgkin-Huxley neurons arranged in a small-world topology using the Watts-Strogatz algorithm is used to generate synthetic electrocorticographic (ECoG) signals. ECoG data from 18 epilepsy patients is used to validate the model. Unsupervised machine learning is used with both patient and synthetic data to identify potential electrophysiologic biomarkers of the preictal period. Results/Findings: The model has shown states corresponding to …

Ischemic And Hemorrhagic Stroke Secondary To Hsv-1 Encephalitis, Fiorella Sotomayor Villanueva, Mounika Angirekula, Martha Baker

Advances in Clinical Medical Research and Healthcare Delivery

Background HSV is the most common cause of encephalitis, and although rare, it can lead to cerebrovascular manifestations such as ischemia or hemorrhage, which can sometimes overlap. The mechanism behind cerebrovascular pathology is not well understood, and further research is needed to fully comprehend it.

Case Report A35-year-old patient that presented with AMS, focal deficit and meningeal signs. Patient was admitted with diagnosis of meningoencephalitis and lumbar puncture (LP) revealed Herpes simplex type 1. Given focal deficit, MRI of the brain was performed and showed presence of multifocal ischemic stroke with associated petechial hemorrhage. After being started on proper therapy, …

Hemiplegic Migraines; A Barrage On The Mind, Ganesh Arun, Omar Siddiqui, Ellen Sampson, Adnaan Sheikh, Harsha Surath, Dayakar Reddy

Advances in Clinical Medical Research and Healthcare Delivery

Hemiplegic migraines (HM) are a rare type of migraine with an aura phase that includes muscle weakness. This form of migraine can either occur sporadically or can be seen in patients with familial hemiplegic migraine which is an autosomal dominant subtype that runs in families. Migraines are classically accompanied by phonophobia, photophobia, neurological symptoms, nausea or vomiting. The subcategory of hemiplegic migraine involves a transient wave of motor weakness and muscle spasms secondary to decreased threshold of excitation in the neurologic system. The etiology of Hemiplegic Migraines is either idiopathic condition or genetic mutation in the CACNA1A, ATP1A2 and SCN1A …

Treatment Of Nonsurgical Refractory Back Pain With High-Frequency Spinal Cord Stimulation At 10 Khz: 12-Month Results Of A Pragmatic, Multicenter, Randomized Controlled Trial., Leonardo Kapural, Jessica Jameson, Curtis Johnson, Daniel Kloster, Aaron Calodney, Peter Kosek, Julie Pilitsis, Markus Bendel, Erika Petersen, Chengyuan Wu, Taissa Cherry, Shivanand P Lad, Cong Yu, Dawood Sayed, Johnathan Goree, Mark K Lyons, Andrew Sack, Diana Bruce, Frances Rubenstein, Rose Province-Azalde, David Caraway, Naresh P Patel

Department of Neurosurgery Faculty Papers

Objective: Spinal cord stimulation (SCS) at 10 kHz (10-kHz SCS) is a safe and effective therapy for treatment of chronic low-back pain. However, it is unclear from existing evidence whether these findings can be generalized to patients with chronic back pain that is refractory to conventional medical management (CMM) and who have no history of spine surgery and are not acceptable candidates for spine surgery. The authors have termed this condition "nonsurgical refractory back pain" (NSRBP) and conducted a multicenter, randomized controlled trial to compare CMM with and without 10-kHz SCS in this population.

Methods: Patients with NSRBP, as defined …

Optimizing The Application Of Surgery For Degenerative Cervical Myelopathy [Ao Spine Recode-Dcm Research Priority Number 10], Ricardo Rodrigues-Pinto, Thiago Montenegro, Benjamin M Davies, So Kato, Yoshiharu Kawaguchi, Manabu Ito, Mehmet Zileli, Brian K Kwon, Michael G Fehlings, Paul A Koljonen, Shekar N Kurpad, James D Guest, Bizhan Aarabi, Vafa Rahimi-Movaghar, Jefferson R Wilson, Mark R N Kotter, James Harrop

Department of Neurosurgery Faculty Papers

Study design: Literature Review (Narrative).

Objective: To introduce the number 10 research priority for Degenerative Cervical Myelopathy: Individualizing Surgery.

Methods: This article summarizes the current recommendations and indications for surgery, including how known prognostic factors such as injury time, age, disease severity, and associated comorbidities impact surgical outcome. It also considers key areas of uncertainty that should be the focus of future research.

Results: While a small proportion of conservatively managed patients may remain stable, the majority will deteriorate over time. To date, surgical decompression is the mainstay of treatment, able to halt disease progression and improve neurologic function and …

Developing Novel Therapies For Degenerative Cervical Myelopathy [Ao Spine Recode-Dcm Research Priority Number 7]: Opportunities From Restorative Neurobiology., Aref-Ali Gharooni, Brian K Kwon, Michael G Fehlings, Timothy F Boerger, Ricardo Rodrigues-Pinto, Paul Aarne Koljonen, Shekar N Kurpad, James Harrop, Bizhan Aarabi, Vafa Rahimi-Movaghar, Jefferson R Wilson, Benjamin M Davies, Mark R N Kotter, James D Guest

Department of Neurosurgery Faculty Papers

Study design: Narrative review.

Objectives: To provide an overview of contemporary therapies for the James Lind Alliance priority setting partnership for degenerative cervical myelopathy (DCM) question: 'Can novel therapies, including stem-cell, gene, pharmacological and neuroprotective therapies, be identified to improve the health and wellbeing of people living with DCM and slow down disease progression?'

Methods: A review of the literature was conducted to outline the pathophysiology of DCM and present contemporary therapies that may hold therapeutic value in 3 broad categories of neuroprotection, neuroregeneration, and neuromodulation.

Results: Chronic spinal cord compression leads to ischaemia, neuroinflammation, demyelination, and neuronal loss. Surgical …

James Lind Alliance Priority Setting Partnership For Degenerative Cervical Myelopathy [Ao Spine Recode-Dcm]: An Overview Of The Methodology Used To Process And Short-List Research Uncertainties, Lindsay Tetreault, Oliver Mowforth, Danyal Z Khan, Toto Gronlund, Philip Garwood, Olesja Hazenbiller, James S Harrop, Bizhan Aarabi, Vafa Rahimi-Movaghar, Shekar N Kurpad, James D Guest, Jefferson R Wilson, Brian K Kwon, Michael G Fehlings, Benjamin M Davies, Mark R N Kotter

Department of Neurosurgery Faculty Papers

Study design: Overview of the methods used for a James Lind Alliance (JLA) Priority Setting Partnership (PSP).

Objectives: The objectives of this article are to (i) provide a brief overview of the JLA-facilitated PSP process; (ii) outline how research uncertainties were initially processed in the AO Spine RECODE-DCM PSP; and (iii) delineate the methods for interim prioritization and the priority setting workshop.

Methods: A steering group was created to define the scope for the PSP, organize its activities, and establish protocols for decision-making. A survey was created asking what questions on the diagnosis, treatment, and long-term management of DCM should …

Establishing Diagnostic Criteria For Degenerative Cervical Myelopathy [Ao Spine Recode-Dcm Research Priority Number 3], Bryn Hilton, Emma L Gardner, Zhilin Jiang, Lindsay Tetreault, Jamie R F Wilson, Carl Moritz Zipser, K Daniel Riew, James D Guest, James Harrop, Michael G Fehlings, Ricardo Rodrigues-Pinto, Vafa Rahimi-Movaghar, Bizhan Aarabi, Paul A Koljonen, Mark R N Kotter, Benjamin M Davies, Brian K Kwon

Department of Neurosurgery Faculty Papers

Study design: Narrative review.

Objectives: To discuss the importance of establishing diagnostic criteria in Degenerative Cervical Myelopathy (DCM), including factors that must be taken into account and challenges that must be overcome in this process.

Methods: Literature review summarising current evidence of establishing diagnostic criteria for DCM.

Results: Degenerative Cervical Myelopathy (DCM) is characterised by a degenerative process of the cervical spine resulting in chronic spinal cord dysfunction and subsequent neurological disability. Diagnostic delays lead to progressive neurological decline with associated reduction in quality of life for patients. Surgical decompression may halt neurologic worsening and, in many cases, improves function. …

Degenerative Cervical Myelopathy: Development And Natural History [Ao Spine Recode-Dcm Research Priority Number 2]., Aria Nouri, Enrico Tessitore, Granit Molliqaj, Torstein Meling, Karl Schaller, Hiroaki Nakashima, Yasutsugu Yukawa, Josef Bednarik, Allan R Martin, Peter Vajkoczy, Joseph S Cheng, Brian K Kwon, Shekar N Kurpad, Michael G Fehlings, James S Harrop, Bizhan Aarabi, Vafa Rahimi-Movaghar, James D Guest, Benjamin M Davies, Mark R N Kotter, Jefferson R Wilson

Department of Neurosurgery Faculty Papers

Study design: Narrative review.

Objectives: To discuss the current understanding of the natural history of degenerative cervical myelopathy (DCM).

Methods: Literature review summarizing current evidence pertaining to the natural history and risk factors of DCM.

Results: DCM is a common condition in which progressive arthritic disease of the cervical spine leads to spinal cord compression resulting in a constellation of neurological symptoms, in particular upper extremity dysfunction and gait impairment. Anatomical factors including cord-canal mismatch, congenitally fused vertebrae and genetic factors may increase individuals' risk for DCM development. Non-myelopathic spinal cord compression (NMSCC) is a common phenomenon with a prevalence …

Developing Peri-Operative Rehabilitation In Degenerative Cervical Myelopathy [Ao Spine Recode-Dcm Research Priority Number 6]: An Unexplored Opportunity?, Timothy F Boerger, Allison S Hyngstrom, Julio C Furlan, Sukhvinder Kalsi-Ryan, Armin Curt, Brian K Kwon, Shekar N Kurpad, Michael G Fehlings, James Harrop, Bizhan Aarabi, Vafa Rahimi-Movaghar, James D Guest, Jefferson R Wilson, Benjamin M Davies, Mark R N Kotter, Paul A Koljonen

Department of Neurosurgery Faculty Papers

Study design: Narrative review.

Objective: Degenerative cervical myelopathy is one of the most frequent impairments of the spinal cord encountered internationally in adults. Currently, surgical decompression is the recommended treatment for people with DCM (PwCM) presenting with moderate to severe symptoms or neurological deficits. However, despite surgical intervention, not all patients make a complete recovery due to the irreversible tissue damage within the spinal cord. The objective of this review is to describe the state and gaps in the current literature on rehabilitation for PwCM and possible innovative rehabilitation strategies.

Methods: Literature search.

Results: In other neurological disorders such as …

A New Framework For Investigating The Biological Basis Of Degenerative Cervical Myelopathy [Ao Spine Recode-Dcm Research Priority Number 5]: Mechanical Stress, Vulnerability And Time, Benjamin M Davies, Oliver Mowforth, Aref-Ali Gharooni, Lindsay Tetreault, Aria Nouri, Rana S Dhillon, Josef Bednarik, Allan R Martin, Adam Young, Hitoshi Takahashi, Timothy F Boerger, Virginia Fj Newcombe, Carl Moritz Zipser, Patrick Freund, Paul Aarne Koljonen, Ricardo Rodrigues-Pinto, Vafa Rahimi-Movaghar, Jefferson R Wilson, Shekar N Kurpad, Michael G Fehlings, Brian K Kwon, James Harrop, James D Guest, Armin Curt, Mark R N Kotter

Department of Neurosurgery Faculty Papers

Study design: Literature Review (Narrative).

Objective: To propose a new framework, to support the investigation and understanding of the pathobiology of DCM, AO Spine RECODE-DCM research priority number 5.

Methods: Degenerative cervical myelopathy is a common and disabling spinal cord disorder. In this perspective, we review key knowledge gaps between the clinical phenotype and our biological models. We then propose a reappraisal of the key driving forces behind DCM and an individual's susceptibility, including the proposal of a new framework.

Results: Present pathobiological and mechanistic knowledge does not adequately explain the disease phenotype; why only a subset of patients with …

Recent Insights Into The Role Of Glia And Oxidative Stress In Alzheimer’S Disease Gained From Drosophila, Lindsey D Goodman, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Here, we discuss findings made using Drosophila on Alzheimer's disease (AD) risk and progression. Recent studies have investigated the mechanisms underlying glia-mediated neuroprotection in AD. First, we discuss a novel mechanism of glial lipid droplet formation that occurs in response to elevated reactive oxygen species in neurons. The data suggest that disruptions to this process contribute to AD risk. We further discuss novel mechanistic insights into glia-mediated Aβ42-clearance made using the fly. Finally, we highlight work that provides evidence that the aberrant accumulation of reactive oxygen species in AD may not just be a consequence of disease but contribute to …

Physical Activity Level And Stroke Risk In Us Population: A Matched Case-Control Study Of 102,578 Individuals, Sherief Ghozy, Ahmad Helmy Zayan, Amr Ehab El-Qushayri, Kate Elizabeth Parker, Joseph Varney, Kevin M. Kallmes, Sara Morsy, Alzhraa Salah Abbas, Jose Danilo B Diestro, Ameer E. Hassan

School of Medicine Publications

Background: Stroke has been linked to a lack of physical activity; however, the extent of the association between inactive lifestyles and stroke risk has yet to be characterized across large populations.

Purpose: This study aimed to explore the association between activity-related behaviors and stroke incidence.

Methods: Data from 1999 to 2018 waves of the concurrent cross-sectional National Health and Nutrition Examination Survey (NHANES) were extracted. We analyzed participants characteristics and outcomes for all participants with data on whether they had a stroke or not and assessed how different forms of physical activity affect the incidence of disease.

Results: Of the …

Antiplatelet Use In Ischemic Stroke, Marharyta Kamarova, Sheharyar Baig, Hamish Patel, Kimberley Monks, Mohammad Wasay, Ali Ali, Jessica Redgrave, Arshad Majid, Simon M. Bell

Section of Neurology

Objective: A literature review of antiplatelet agents for primary and secondary stroke prevention, including mechanism of action, cost, and reasons for lack of benefit.
Data sources: Articles were gathered from MEDLINE, Cochrane Reviews, and PubMed databases (1980-2021). Abstracts from scientific meetings were considered. Search terms included ischemic stroke, aspirin, clopidogrel, dipyridamole, ticagrelor, cilostazol, prasugrel, glycoprotein IIb/IIIa inhibitors.
Study selection and data extraction: English-language original and review articles were evaluated. Guidelines from multiple countries were reviewed. Articles were evaluated independently by 2 authors.
Data synthesis: An abundance of evidence supports aspirin and clopidogrel use for secondary stroke prevention. In the acute …

Pathogenic Tnf-Α Drives Peripheral Nerve Inflammation In An Aire-Deficient Model Of Autoimmunity, Yan Wang, Lily Guo, Xihui Yin, Ethan C Mccarthy, Mandy I Cheng, Aline T Hoang, Ho-Chung Chen, Anushi Y Patel, Denise Allard Trout, Erin Xu, Natalie Yakobian, Willy Hugo, James F Howard, Katherine M Sheu, Alexander Hoffmann, Melissa G Lechner, Maureen A Su

Department of Neurology Faculty Papers

Immune cells infiltrate the peripheral nervous system (PNS) after injury and with autoimmunity, but their net effect is divergent. After injury, immune cells are reparative, while in inflammatory neuropathies (e.g., Guillain Barré Syndrome and chronic inflammatory demyelinating polyneuropathy), immune cells are proinflammatory and promote autoimmune demyelination. An understanding of immune cell phenotypes that distinguish these conditions may, therefore, reveal new therapeutic targets for switching immune cells from an inflammatory role to a reparative state. In an autoimmune regulator (Aire)-deficient mouse model of inflammatory neuropathy, we used single-cell RNA sequencing of sciatic nerves to discover a transcriptionally heterogeneous cellular landscape, including …

Disruption Of Mecp2-Tcf20 Complex Underlies Distinct Neurodevelopmental Disorders, Jian Zhou, Hamdan Hamdan, Hari Krishna Yalamanchili, Kaifang Pang, Amy E Pohodich, Joanna Lopez, Yingyao Shao, Juan A Oses-Prieto, Lifang Li, Wonho Kim, Mark A Durham, Sameer S Bajikar, Donna J Palmer, Philip Ng, Michelle L Thompson, E Martina Bebin, Amelie J Müller, Alma Kuechler, Antje Kampmeier, Tobias B Haack, Alma L Burlingame, Zhandong Liu, Matthew N Rasband, Huda Y Zoghbi

Duncan NRI Faculty and Staff Publications

MeCP2 is associated with Rett syndrome (RTT), MECP2 duplication syndrome, and a number of conditions with isolated features of these diseases, including autism, intellectual disability, and motor dysfunction. MeCP2 is known to broadly bind methylated DNA, but the precise molecular mechanism driving disease pathogenesis remains to be determined. Using proximity-dependent biotinylation (BioID), we identified a transcription factor 20 (TCF20) complex that interacts with MeCP2 at the chromatin interface. Importantly, RTT-causing mutations in MECP2 disrupt this interaction. TCF20 and MeCP2 are highly coexpressed in neurons and coregulate the expression of key neuronal genes. Reducing Tcf20 partially rescued the behavioral deficits caused …