Medicine and Health Sciences Commons^™

Igg4-Mediated Neurologic Autoimmunities: Understanding The Pathogenicity Of Igg4, Ineffectiveness Of Ivig, And Long-Lasting Benefits Of Anti-B Cell Therapies, Marinos Dalakas

Department of Neurology Faculty Papers

Background and objectives: Describe the unique functions of immunoglobulin G4 (IgG4) in IgG4-neurologic disorders (IgG4-ND) and explain why, in contrast to their IgG1-counterparts, they respond poorly to intravenous immune globulin (IVIg) but effectively to anti-B cell therapies.

Methods: The IgG4 structure and isotype switch, B cells and plasmablasts relevant to IgG4 production, and IgG4-induced disruption of the targeted antigens are reviewed and compared with IgG1-mediated autoimmune ND, where IVIg inhibits IgG1-triggered inflammatory effects.

Results: The main IgG4-ND include muscle-specific kinase myasthenia; nodal/paranodal chronic inflammatory demyelinating polyradiculoneuropathy with antibodies to neurofascin-155, contactin-1/caspr-1, or pan-neurofascins; antileucine-rich, glioma-inactivated-1 and contactin-associated protein-like 2 associated-limbic …

Efficacy And Safety Of Fremanezumab In Clinical Trial Participants Aged ≥60 Years With Episodic Or Chronic Migraine: Pooled Results From 3 Randomized, Double-Blind, Placebo-Controlled Phase 3 Studies, Stephanie J. Nahas, Steffen Naegel, Joshua M Cohen, Xiaoping Ning, Lindsay Janka, Verena Ramirez Campos, Lynda J Krasenbaum, Dagny Holle-Lee, David Kudrow, Christian Lampl

Department of Neurology Faculty Papers

Background: Although migraine is less common in older people, preventive treatment of migraine in these individuals may be more challenging due to the presence of multiple comorbidities and polypharmacy. Additionally, evidence for migraine treatment efficacy, safety, and tolerability is limited in this population. We evaluated efficacy, safety, and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), in clinical trial participants aged ≥60 years with episodic migraine (EM) or chronic migraine (CM).

Methods: This analysis included data from 3 randomized, double-blind, placebo-controlled phase 3 studies: the HALO EM study, HALO CM study, and …

Risk Factors Associated With Long Covid Syndrome: A Retrospective Study, A A Asadi-Pooya, Ali Akbari, Amir Emami, Mehrzad Lotfi, Mahtab Rostamihosseinkhani, Hamid Nemati, Zohreh Barzegar, Maryam Kabiri, Zahra Zeraatpisheh, Mohsen Farjoud-Kouhanjani, Anahita Jafari, Fateme Sasannia, Shayan Ashrafi, Masoume Nazeri, Sara Nasiri, Mina Shahisavandi

Department of Neurology Faculty Papers

Background: Recently, people have recognized the post-acute phase symptoms of the COVID-19. We investigated the long-term symptoms associated with COVID-19, (Long COVID Syndrome), and the risk factors associated with it. Methods: This was a retrospective observational study. All the consecutive adult patients referred to the healthcare facilities anywhere in Fars province from 19 February 2020 until 20 November 2020 were included. All the patients had a confirmed COVID-19 diagnosis. In a phone call to the patients, at least three months after their discharge from the hospital, we obtained their current information. The IBM SPSS Statistics (version 25.0) was used. Pearson …

Accuracy Of High-Frequency Oscillations Recorded Intraoperatively For Classification Of Epileptogenic Regions., Shennan A Weiss, Richard J Staba, Ashwini Sharan, Chengyuan Wu, Daniel Y. Rubinstein, Sandhitsu Das, Zachary J. Waldman, Iren Orosz, Gregory Worrell, Jerome Engel, Michael R Sperling

Department of Neurology Faculty Papers

To see whether acute intraoperative recordings using stereo EEG (SEEG) electrodes can replace prolonged interictal intracranial EEG (iEEG) recording, making the process more efficient and safer, 10 min of iEEG were recorded following electrode implantation in 16 anesthetized patients, and 1–2 days later during non-rapid eye movement (REM) sleep. Ripples on oscillations (RonO, 80–250 Hz), ripples on spikes (RonS), sharp-spikes, fast RonO (fRonO, 250–600 Hz), and fast RonS (fRonS) were semi-automatically detected. HFO power and frequency were compared between the conditions using a generalized linear mixed-effects model. HFO rates were compared using a two-way repeated measures ANOVA with anesthesia type …

Contributions Of Iranian Journal Of Medical Sciences (Ijms) During The Covid-19 Pandemic., A A Asadi-Pooya, Mohsen Farazdaghi, Marzieh Rostaminejad, Manica Negahdaripour

Department of Neurology Faculty Papers

No abstract provided.

Multiple-Brain Systems Dynamically Interact During Tonic And Phasic States To Support Language Integrity In Temporal Lobe Epilepsy, Shilpi Modi, Xiaosong He, Kapil Chaudhary, Walter Hinds, Andrew Crow, Ashithkumar Beloor-Suresh, Michael R Sperling, Joseph I Tracy

Department of Neurology Faculty Papers

An epileptogenic focus in the dominant temporal lobe can result in the reorganization of language systems in order to compensate for compromised functions. We studied the compensatory reorganization of language in the setting of left temporal lobe epilepsy (TLE), taking into account the interaction of language (L) with key non-language (NL) networks such as dorsal attention (DAN), fronto-parietal (FPN) and cingulo-opercular (COpN), with these systems providing cognitive resources helpful for successful language performance. We applied tools from dynamic network neuroscience to functional MRI data collected from 23 TLE patients and 23 matched healthy controls during the resting state (RS) and …

Electroencephalography In Patients With Autism Spectrum Disorder, A A Asadi-Pooya

Department of Neurology Faculty Papers

No abstract provided.

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 …

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 …

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

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 …

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

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

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

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

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. …

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

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

Department of Neurology Faculty Papers

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

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 …

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 …

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

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 …

Long Term Safety, Tolerability, And Efficacy Of Intracutaneous Zolmitriptan (M207) In The Acute Treatment Of Migraine., Stephanie J. Nahas, Nada Hindiyeh, Deborah I. Friedman, Nada Elbuluk, Donald J. Kellerman, Pamela K. Foreman, Peter Schmidt

Department of Neurology Faculty Papers

OBJECTIVE: To determine the long-term safety and tolerability profile of M207 in the acute treatment of migraine.

BACKGROUND: M207 is an investigational microneedle-based system for intracutaneous delivery of zolmitriptan for the treatment of migraine attacks. Following on the positive results of a Phase 2/3 placebo-controlled efficacy study (ZOTRIP), this study was designed to evaluate the safety of this novel product during repeated use for the treatment of migraine attacks.

METHODS: In this 6-12 month open-label, multicenter observational study, participants used an eDiary to record headache symptoms and adverse events at specified intervals up to 48 h following treatment of a …

Automated Analysis Of Risk Factors For Postictal Generalized Eeg Suppression, Xiuhe Zhao, Laura Vilella, Liang Zhu, M R Sandhya Rani, Johnson P Hampson, Jaison Hampson, Norma J Hupp, Rup K Sainju, Daniel Friedman, Maromi Nei, Catherine Scott, Luke Allen, Brian K Gehlbach, Stephan Schuele, Ronald M Harper, Beate Diehl, Lisa M Bateman, Orrin Devinsky, George B Richerson, Guo-Qiang Zhang, Samden D Lhatoo, Nuria Lacuey

Department of Neurology Faculty Papers

Rationale: Currently, there is some ambiguity over the role of postictal generalized electro-encephalographic suppression (PGES) as a biomarker in sudden unexpected death in epilepsy (SUDEP). Visual analysis of PGES, known to be subjective, may account for this. In this study, we set out to perform an analysis of PGES presence and duration using a validated signal processing tool, specifically to examine the association between PGES and seizure features previously reported to be associated with visually analyzed PGES. Methods: This is a prospective, multicenter epilepsy monitoring study of autonomic and breathing biomarkers of SUDEP in adult patients with intractable epilepsy. We …

Lack Of Observed Tolerance To Diazepam Nasal Spray (Valtoco®) After Long-Term Rescue Therapy In Patients With Epilepsy: Interim Results From A Phase 3, Open-Label, Repeat-Dose Safety Study., Gregory D. Cascino, Daniel Tarquinio, James W. Wheless, R. Edward Hogan, Michael R. Sperling, Kore Liow, Jay Desai, Charles Davis, Adrian L. Rabinowicz, Enrique Carrazana

Department of Neurology Faculty Papers

OBJECTIVE: Tolerance is a known consideration for maintenance use of benzodiazepines and other antiseizure drugs; however, clinical experience suggests that tolerance may not be anticipated with long-term intermittent use of benzodiazepines as rescue therapy. Diazepam nasal spray (Valtoco®) is a proprietary intranasal formulation approved for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in patients with epilepsy aged ≥6 years. Reported here are exploratory analyses investigating whether there was evidence of development of tolerance in an interim analysis of a long-term, phase 3, open-label safety study of diazepam nasal spray.

METHODS: …

Gad Antibody-Spectrum Disorders: Progress In Clinical Phenotypes, Immunopathogenesis And Therapeutic Interventions., Popianna Tsiortou, Harry Alexopoulos, Marinos Dalakas

Department of Neurology Faculty Papers

Antibodies against glutamic acid decarboxylase (GAD), originally linked to stiff person syndrome (SPS), now denote the “GAD antibody-spectrum disorders” (GAD-SD) that also include autoimmune epilepsy, limbic encephalitis, cerebellar ataxia and nystagmus with overlapping symptomatology highlighting autoimmune neuronal excitability disorders. The reasons for the clinical heterogeneity among GAD-antibody associated syndromes remain still unsettled, implicating variable susceptibility of GABAergic neurons to anti-GAD or other still unidentified autoantibodies. Although anti-GAD antibody titers do not correlate with clinical severity, very high serum titers, often associated with intrathecal synthesis of anti-GAD-specific IgG, point to in-situ effects of GAD or related autoantibodies within the central nervous …

Crispr-Mediated Rapid Generation Of Neural Cell-Specific Knockout Mice Facilitates Research In Neurophysiology And Pathology., Dan Xiao, Weifeng Zhang, Qing Wang, Xing Li, Yuan Zhang, Javad Rasouli, Giacomo Casella, Bogoljub Ciric, Mark Curtis, A M Rostami, Guang-Xian Zhang

Department of Neurology Faculty Papers

Inducible conditional knockout mice are important tools for studying gene function and disease therapy, but their generation is costly and time-consuming. We introduced clustered regularly interspaced short palindromic repeats (CRISPR) and Cre into an LSL-Cas9 transgene-carrying mouse line by using adeno-associated virus (AAV)-PHP.eB to rapidly knockout gene(s) specifically in central nervous system (CNS) cells of adult mice. NeuN in neurons and GFAP in astrocytes were knocked out 2 weeks after an intravenous injection of vector, with an efficiency comparable to that of inducible Cre-loxP conditional knockout. For functional testing, we generated astrocyte-specific Act1 knockout mice, which exhibited a phenotype …

Cardiovascular Disease Risk, Awareness, And Treatment In People With Epilepsy, Samuel W Terman, Carole E Aubert, Chloe E Hill, Jeremy Skvarce, James F Burke, Scott Mintzer

Department of Neurology Faculty Papers

OBJECTIVE: To evaluate whether cardiovascular risk, risk awareness, and guideline concordant treatment differ in individuals with versus without epilepsy.

METHODS: This was a retrospective cross-sectional study using the National Health and Nutrition Examination Survey. We included participants ≥18 years for 2013-2018. We classified participants as having epilepsy if reporting ≥1 medication treating seizures. We calculated 10-year atherosclerotic cardiovascular disease (ASCVD) risk using the revised pooled cohort equation. We compared unadjusted and adjusted risk for participants with versus without epilepsy. We then assessed hypertension and diabetes disease awareness and control, plus statin guideline-concordance. We assessed mediators for both ASCVD risk and …

Can Early Treatment Of Twitcher Mice With High Dose Aavrh10-Galc Eliminate The Need For Bmt?, Mohammad Rafi, Paola Luzi, David A Wenger

Department of Neurology Faculty Papers

Introduction: Krabbe disease (KD) is an autosomal recessive disorder caused by mutations in the galactocerebrosidase (GALC) gene resulting in neuro-inflammation and defective myelination in the central and peripheral nervous systems. Most infantile patients present with clinical features before six months of age and die before two years of age. The only treatment available for pre-symptomatic or mildly affected individuals is hematopoietic stem cell transplantation (HSCT). In the animal models, combining bone marrow transplantation (BMT) with gene therapy has shown the best results in disease outcome. In this study, we examine the outcome of gene therapy alone.

Methods: Twitcher (twi) mice …