Department of Neurology Specialty Group Publications

Risk Factors For MACE And Bleeding In Atrial Fibrillation Patients Undergoing Surgery: Insights From The Bridge Trial

sábado, junio 29, 2024

Author(s): Liqi Shu,Naomi Jack,Adam de Havenon,Eric D Goldstein,Farhan Khan,Thanh N Nguyen,Nils Henninger,James E Siegler,Christoph Stretz,Elizabeth Perelstein,Narendra Kala,Maheen Rana,Karen L Furie,James D Douketis,Shadi Yaghi

Source: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association

CONCLUSION: -We identified predictors for MACE and symptomatic bleeding in AF patients undergoing elective procedures. These insights may help guide perioperative decisions to reduce the risk of adverse outcomes.

New Imaging Markers in Multiple Sclerosis and Related Disorders: Smoldering Inflammation and the Central Vein Sign

viernes, junio 28, 2024

Author(s): Christopher C Hemond,María I Gaitán,Martina Absinta,Daniel S Reich

Source: Neuroimaging clinics of North America

Concepts of multiple sclerosis (MS) biology continue to evolve, with observations such as "progression independent of disease activity" challenging traditional phenotypic categorization. Iron-sensitive, susceptibility-based imaging techniques are emerging as highly translatable MR imaging sequences that allow for visualization of at least 2 clinically useful biomarkers: the central vein sign and the paramagnetic rim lesion (PRL). Both biomarkers demonstrate high specificity in the discrimination...

The exocyst subunit EXOC2 regulates the toxicity of expanded GGGGCC repeats in C9ORF72-ALS/FTD

jueves, junio 27, 2024

Author(s): Dilara O Halim,Gopinath Krishnan,Evan P Hass,Soojin Lee,Mamta Verma,Sandra Almeida,Yuanzheng Gu,Deborah Y Kwon,Thomas G Fazzio,Fen-Biao Gao

Source: Cell reports

GGGGCC (G(4)C(2)) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How this genetic mutation leads to neurodegeneration remains largely unknown. Using CRISPR-Cas9 technology, we deleted EXOC2, which encodes an essential exocyst subunit, in induced pluripotent stem cells (iPSCs) derived from C9ORF72-ALS/FTD patients. These cells are viable owing to the presence of truncated EXOC2, suggesting that exocyst...

Focused Ultrasound-Mediated Disruption of the Blood-Brain Barrier for AAV9 Delivery in a Mouse Model of Huntington's Disease

jueves, junio 27, 2024

Author(s): Bernie S Owusu-Yaw,Yongzhi Zhang,Lilyan Garrett,Alvin Yao,Kai Shing,Ana Rita Batista,Miguel Sena-Esteves,Jaymin Upadhyay,Kimberly Kegel-Gleason,Nick Todd

Source: Pharmaceutics

Huntington's disease (HD) is a monogenic neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the HTT gene. There are no cures for HD, but the genetic basis of this disorder makes gene therapy a viable approach. Adeno-associated virus (AAV)-miRNA-based therapies have been demonstrated to be effective in lowering HTT mRNA; however, the blood-brain barrier (BBB) poses a significant challenge for gene delivery to the brain. Delivery strategies...

Neurologic Care for Transgender and Gender-Diverse People: A Review of Current Evidence and Clinical Implications

miércoles, junio 26, 2024

Author(s): Gwen Zeigler,Cole A Harrington,Nicole Rosendale,Christos Ganos,Valeria Roldan,Anna Pace,Sasha Alick-Lindstrom,Casey Orozco-Poore,Wissam Deeb,Margaret L Hansen,Z Paige L'Erario

Source: Neurology. Clinical practice

PURPOSE OF REVIEW: To summarize the literature on neurologic care for transgender and gender-diverse (TGD) people and provide implications for clinical practice.

A single-arm, open-label pilot study of neuroimaging, behavioral, and peripheral inflammatory correlates of mindfulness-based stress reduction in multiple sclerosis

martes, junio 18, 2024

Author(s): Christopher C Hemond,Mugdha Deshpande,Idanis Berrios-Morales,Shaokuan Zheng,Jerrold S Meyer,George M Slavich,Steven W Cole

Source: Scientific reports

Multiple sclerosis (MS) is a chronic neurological disease frequently associated with significant fatigue, anxiety, depression, and stress. These symptoms are difficult to treat, and prominently contribute to the decreases in quality of life observed with MS. The underlying mechanisms of these "silent" symptoms are not well understood and include not just the psychological responses to a chronic disease, but also biological contributions from bidirectional psycho-neuro-immune (dys)regulation of...

AAV9-Mediated Intra-Striatal Delivery of GNAO1 Reduces Hyperlocomotion in Gnao1 Heterozygous R209H Mutant Mice

miércoles, junio 12, 2024

Author(s): Alex J Roy,Jeffrey R Leipprandt,Joseph R Patterson,Anna C Stoll,Christopher J Kemp,Zaipo-Tcheisian D Oula,Tyler Mola,Ana R Batista,Caryl E Sortwell,Miguel Sena-Esteves,Richard R Neubig

Source: The Journal of pharmacology and experimental therapeutics

Mutations in the GNAO1 gene, which encodes the abundant brain G-protein Gα(o), result in neurologic disorders characterized by developmental delay, epilepsy, and movement abnormalities. There are over 50 mutant alleles associated with GNAO1 disorders; the R209H mutation results in dystonia, choreoathetosis, and developmental delay without seizures. Mice heterozygous for the human mutant allele (Gnao1 ^(+/R209H)) exhibit hyperactivity in open field tests but no seizures. We developed...

Systematic rare variant analyses identify RAB32 as a susceptibility gene for familial Parkinson's disease

lunes, junio 10, 2024

Author(s): Paul J Hop,Dongbing Lai,Pamela J Keagle,Desiree M Baron,Brendan J Kenna,Maarten Kooyman,None Shankaracharya,Cheryl Halter,Letizia Straniero,Rosanna Asselta,Salvatore Bonvegna,Alexandra I Soto-Beasley,Project MinE ALS Sequencing Consortium,Zbigniew K Wszolek,Ryan J Uitti,Ioannis Ugo Isaias,Gianni Pezzoli,Nicola Ticozzi,Owen A Ross,Jan H Veldink,Tatiana M Foroud,Kevin P Kenna,John E Landers

Source: Nature genetics

Despite substantial progress, causal variants are identified only for a minority of familial Parkinson's disease (PD) cases, leaving high-risk pathogenic variants unidentified^(1,2). To identify such variants, we uniformly processed exome sequencing data of 2,184 index familial PD cases and 69,775 controls. Exome-wide analyses converged on RAB32 as a novel PD gene identifying c.213C G/p.S71R as a high-risk variant presenting in ~0.7% of familial PD cases while observed in only 0.004% of...

Anticoagulation Versus Antiplatelets in Spontaneous Cervical Artery Dissection: A Systematic Review and Meta-Analysis

viernes, junio 07, 2024

Author(s): Shadi Yaghi,Liqi Shu,Lauren Fletcher,Fayez H Fayad,Asghar Shah,Ana Herning,Noail Isho,Perla Mansour,Kareem Joudi,Bashar Zaidat,Noor A Mahmoud,Feras Abdul Khalek,Han Xiao,Eric Goldstein,Malik Ghannam,James E Siegler,Setareh Salehi Omran,Ekaterina Bakradze,Thanh N Nguyen,Zafer Keser,Muhib Khan,Reza Bavarsad Shahripour,Adam de Havenon,Nils Henninger,Mirjam R Heldner,Thalia S Field,Yasmin Aziz,Eva A Mistry,Karen Furie,Stefan Engelter,Hugh S Markus

Source: Stroke

CONCLUSIONS: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.

Appendicular lean mass index and motor function in ambulatory patients with Duchenne muscular dystrophy

miércoles, junio 05, 2024

Author(s): Michael Kiefer,Elise Townsend,Celina Goncalves,K Courtney Shellenbarger,Perman Gochyyev,Brenda L Wong

Source: Muscle & nerve

INTRODUCTION/AIMS: Appendicular lean mass index (ALMI) has been linked to motor function in patients with Duchenne muscular dystrophy (DMD). However, quantification of the relationship between ALMI and disease-specific clinical outcome assessment trajectories is needed. The purpose of this study was to determine associations between dual-energy x-ray absorptiometry (DXA) derived estimates of ALMI and motor function in ambulatory patients with DMD.

Prevalence and Associations of Dural Arteriovenous Fistulae in Cerebral Venous Thrombosis: Analysis of ACTION-CVT

miércoles, junio 05, 2024

Author(s): Aaron Shoskes,Liqi Shu,Thanh N Nguyen,Mohamad Abdalkader,James Giles,Jordan Amar,James E Siegler,Nils Henninger,Marwa ElNazeir,Sami Al Kasab,Piers Klein,Mirjam R Heldner,Kateryna Antonenko,Marios Psychogios,David S Liebeskind,Thalia Field,Ava Liberman,Charles Esenwa,Alexis Simpkins,Grace Li,Jennifer Frontera,Lindsey Kuohn,Aaron Rothstein,Ossama Khazaal,Yasmin Aziz,Eva Mistry,Pooja Khatri,Setareh Salehi Omran,Adeel S Zubair,Richa Sharma,Robert M Starke,Jacques J Morcos,Jose G Romano,Shadi Yaghi,Negar Asdaghi

Source: Journal of stroke

No abstract

Functional trajectories before and after loss of ambulation in Duchenne muscular dystrophy and implications for clinical trials

lunes, junio 03, 2024

Author(s): Craig M McDonald,James Signorovitch,Eugenio Mercuri,Erik H Niks,Brenda Wong,Mirko Fillbrunn,Gautam Sajeev,Erica Yim,Ibrahima Dieye,Debra Miller,Susan J Ward,Nathalie Goemans,Investigators from the PRO-DMD-01 Study, Collaborative Trajectory Analysis Project (cTAP)

Source: PloS one

This study examined functional trajectories of subjects during the transition phase between ambulatory and non-ambulatory Duchenne muscular dystrophy (DMD) to inform clinical trial designs for new therapeutics. Ambulatory, pulmonary, and upper limb function leading up to loss of ambulation (LoA) and non-ambulatory measures following LoA were quantified; time ordering of pulmonary and upper limb milestones relative to LoA were determined; and the 10-second time threshold for 10-meter walk/run...

Cerebral venous sinus thrombosis associated with cancer: analysis of the ACTION-CVT study

domingo, junio 02, 2024

Author(s): Maria Cristina Vedovati,Liqi Shu,Nils Henninger,Adeel S Zubair,Mirjam R Heldner,Sami Al Kasab,James E Siegler,David S Liebeskind,Kateryna Antonenko,Shadi Yaghi,Maurizio Paciaroni

Source: Journal of thrombosis and thrombolysis

Nearly one fifth of patients with venous thromboembolism (VTE) have cancer. When both of these conditions occur, especially in cases of cerebral vein thrombosis (CVT), patient management is often challenging. The aim of this study was to compare the characteristics and event courses in patients affected by CVT with and without cancer. Consecutive patients with CVT from the ACTION-CVT cohort study were included if cancer status was reported. Risk factors as well as the clinical and radiological...

Hypoperfusion Intensity Ratio is Associated with Early Neurologic Deficit Severity and Deterioration after Mechanical Thrombectomy in Large-Vessel Occlusion Ischemic Stroke

jueves, mayo 30, 2024

Author(s): Małgorzata M Miller,Brian Wideman,Muhib Khan,Nils Henninger

Source: AJNR. American journal of neuroradiology

CONCLUSIONS: The hypoperfusion intensity ratio ≥ 0.54 was independently associated with a worse 24-hour post-mechanical thrombectomy NIHSS score and early neurologic deterioration in LVO, but not in DMVO acute ischemic stroke. Pending confirmation in future, prospective studies assessing the hypoperfusion intensity ratio may help identify patients at risk of secondary decline to improve peri-thrombectomy care and clinical decision-making.

Establishment of a Biorepository for Down Syndrome: Experience of the Inter-Institutional Multidisciplinary BioBank - BioBIM

lunes, mayo 27, 2024

Author(s): Claudia Condoluci,Raffaele Palmirotta,Jeanne B Lawrence,Kelly P Smith,Anna R Casini,Gabriella Di Girolamo,Lucia A Majolini,Maria G Valente,Antonella Spila,Chiara Miele,Patrizia Ferroni,Fiorella Guadagni

Source: Discovery medicine

CONCLUSION: By establishing this biobank, we have gathered a significant number of biological samples and clinical data from individuals with Down syndrome, thereby fostering collaboration between different research groups in an open and transparent manner. Sharing expertise and resources among scientists will ultimately facilitate the transfer of knowledge to clinical practice, leading to the development of more effective therapeutic treatments to improve the outcomes and quality of life of...

Measurement of Cost of Boarding in the Emergency Department Using Time-Driven Activity-Based Costing

sábado, mayo 25, 2024

Author(s): Maureen M Canellas,Marcella Jewell,Jennifer L Edwards,Danielle Olivier,Adalia H Jun-O'Connell,Martin A Reznek

Source: Annals of emergency medicine

CONCLUSION: Using advanced cost-accounting methods, our investigation provides novel evidence that boarding of admitted patients is financially costly, adding greater urgency for elimination of this practice.

How to Cure Alzheimer's Disease

viernes, mayo 24, 2024

Author(s): Andrzej W Przybyszewski,Artur Chudzik

Source: Journal of Alzheimer's disease : JAD

There has been a lot of buzz surrounding new drug discoveries that claim to cure Alzheimer's disease (AD). However, it is crucial to keep in mind that the changes in the brain linked to AD start occurring 20-30 years before the first symptoms arise. By the time symptoms become apparent, many areas of the brain have already been affected. That's why experts are focusing on identifying the onset of the neurodegeneration processes to prevent or cure AD effectively. Scientists use biomarkers and...

Interprofessional reconstruction of a policy for academic advancement: The evolution and evaluation of scholarship for today, tomorrow, and beyond

miércoles, mayo 22, 2024

Author(s): Janet Fraser Hale,Luanne Thorndyke,Robert J Milner,Joan Vitello-Cicciu

Source: Journal of professional nursing : official journal of the American Association of Colleges of Nursing

Within higher education, scholarship is narrowly and inconsistently defined, limiting recognition of evolving faculty expectations, particularly for nursing faculty. At this academic medical center, a campus-wide, multi-school, academic advancement policy was achieved with a broader definition of scholarship that included: peer-reviewed publication of federally funded research, as well as innovation in curriculum development, teaching methodology, community engagement, safety and quality...

Mutations in the tail and rod domains of the neurofilament heavy-chain gene increase the risk of ALS

miércoles, mayo 22, 2024

Author(s): Heather Marriott,Thomas P Spargo,Ahmad Al Khleifat,Peter M Andersen,Nazli A Başak,Johnathan Cooper-Knock,Philippe Corcia,Philippe Couratier,Mamede de Carvalho,Vivian Drory,Marc Gotkine,John E Landers,Russell McLaughlin,Jesús S Mora Pardina,Karen E Morrison,Susana Pinto,Christopher E Shaw,Pamela J Shaw,Vincenzo Silani,Nicola Ticozzi,Philip van Damme,Leonard H van den Berg,Patrick Vourc'h,Markus Weber,Jan H Veldink,Project MinE ALS Sequencing Consortium,Richard J Dobson,Patrick Schwab,Ammar Al-Chalabi,Alfredo Iacoangeli

Source: Annals of clinical and translational neurology

OBJECTIVE: Neurofilament heavy-chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk.

Correction to: Clinical characteristics and risk factors for bilateral lateral geniculate body pathology: a systematic review of the literature

jueves, mayo 16, 2024

Author(s): Bahadar S Srichawla,Raymond M Catton,Alexander A Lichtenberg,Nils Henninger

Source: Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

No abstract

Outcomes of mechanical thrombectomy in anticoagulated patients with acute distal and medium vessel stroke

viernes, mayo 10, 2024

Author(s): Hamza Salim,Basel Musmar,Nimer Adeeb,Vivek Yedavalli,Dhairya Lakhani,Sahibjot Singh Grewal,Kareem El Naamani,Nils Henninger,Sri Hari Sundararajan,Anna Luisa Kühn,Jane Khalife,Sherief Ghozy,Luca Scarcia,Benjamin Yq Tan,Robert W Regenhardt,Jeremy J Heit,Nicole M Cancelliere,Joshua D Bernstock,Aymeric Rouchaud,Jens Fiehler,Sunil Sheth,Ajit S Puri,Christian Dyzmann,Marco Colasurdo,Xavier Barreau,Leonardo Renieri,João Pedro Filipe,Pablo Harker,Răzvan Alexandru Radu,Mohamad Abdalkader,Piers Klein,Thomas R Marotta,Julian Spears,Takahiro Ota,Ashkan Mowla,Pascal Jabbour,Arundhati Biswas,Frédéric Clarençon,James E Siegler,Thanh N Nguyen,Ricardo Varela,Amanda Baker,Muhammed Amir Essibayi,David Altschul,Nestor R Gonzalez,Markus A Möhlenbruch,Vincent Costalat,Benjamin Gory,Christian Paul Stracke,Mohammad Ali Aziz-Sultan,Constantin Hecker,Hamza Shaikh,David S Liebeskind,Alessandro Pedicelli,Andrea M Alexandre,Illario Tancredi,Tobias D Faizy,Erwah Kalsoum,Boris Lubicz,Aman B Patel,Vitor Mendes Pereira,Adrien Guenego,Adam A Dmytriw,MAD MT Investigators

Source: European stroke journal

CONCLUSION: Anticoagulated patients undergoing MT for AIS due to DMVO did not show significant differences in 90-day mRS outcomes, reperfusion, or hemorrhage compared to non-anticoagulated patients after adjustment for covariates.

Promoting Growth in Behavioral Neurology: A Path Forward

miércoles, mayo 08, 2024

Author(s): James R Bateman,Sylvia Josephy-Hernandez,Liana G Apostolova,Sheldon Benjamin,A M Barrett,Bradley F Boeve,Andrew E Budson,Zeina Chemali,Chi-Ying R Lin,Kirk R Daffner,Michael D Geschwind,Kenneth M Heilman,Argye E Hillis,Samantha K Holden,Michael S Jaffee,Isaiah Kletenik,Marissa Natelson Love,Lauren R Moo,Victoria S Pelak,Daniel Z Press,Liliana Ramirez-Gomez,Howie J Rosen,Jeremy D Schmahmann,Sanjeev N Vaishnavi,Charles C Windon,Roy H Hamilton,David L Perez

Source: Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of...

A Magnetic Actuator Device for Fully Automated Blinking in Total Bidirectional Eyelid Paralysis: First Proof of Concept in a Human Participant

jueves, mayo 02, 2024

Author(s): Kevin E Houston,Manarshhjot Singh,Ashkan E Sedeh,Eleftherios I Paschalis

Source: Translational vision science & technology

CONCLUSIONS: FEA simulation results conformed to the experimentally observed trend, further supporting the proof of concept and design parameters. This is the first viable approach in human patients with proof of concept for complete reanimation of a bidirectionally paretic eyelid. Further study is warranted to refine the prototype and determine the feasibility and safety of prolonged use.

Outcomes with General Anesthesia Compared to Conscious Sedation for Endovascular Treatment of Medium Vessel Occlusions: Results of an International Multicentric Study

martes, abril 30, 2024

Author(s): Răzvan Alexandru Radu,Vincent Costalat,Michele Romoli,Basel Musmar,James E Siegler,Sherief Ghozy,Jane Khalife,Hamza Salim,Hamza Shaikh,Nimer Adeeb,Hugo H Cuellar-Saenz,Ajith J Thomas,Ramanathan Kadirvel,Mohamad Abdalkader,Piers Klein,Thanh N Nguyen,Jeremy J Heit,Robert W Regenhardt,Joshua D Bernstock,Aman B Patel,James D Rabinov,Christopher J Stapleton,Nicole M Cancelliere,Thomas R Marotta,Vitor Mendes Pereira,Kareem El Naamani,Abdelaziz Amllay,Stavropoula I Tjoumakaris,Pascal Jabbour,Lukas Meyer,Jens Fiehler,Tobias D Faizy,Helena Guerreiro,Anne Dusart,Flavio Bellante,Géraud Forestier,Aymeric Rouchaud,Charbel Mounayer,Anna Luisa Kühn,Ajit S Puri,Christian Dyzmann,Peter T Kan,Marco Colasurdo,Gaultier Marnat,Jérôme Berge,Xavier Barreau,Igor Sibon,Simona Nedelcu,Nils Henninger,Takahiro Ota,Shogo Dofuku,Leonard L L Yeo,Benjamin Yq Tan,Anil Gopinathan,Juan Carlos Martinez-Gutierrez,Sergio Salazar-Marioni,Sunil Sheth,Leonardo Renieri,Carolina Capirossi,Ashkan Mowla,Lina M Chervak,Achala Vagal,Priyank Khandelwal,Arundhati Biswas,Frédéric Clarençon,Mahmoud Elhorany,Kevin Premat,Iacopo Valente,Alessandro Pedicelli,Andrea M Alexandre,João Pedro Filipe,Ricardo Varela,Miguel Quintero-Consuegra,Nestor R Gonzalez,Markus A Ymd,Jessica Jesser,Charlotte Weyland,Adrien Ter Schiphorst,Vivek Yedavalli,Pablo Harker,Yasmin Aziz,Benjamin Gory,Christian Paul Stracke,Constantin Hecker,Monika Killer-Oberpfalzer,Christoph J Griessenauer,Cheng-Yang Hsieh,David S Liebeskind,Illario Tancredi,Robert Fahed,Boris Lubicz,Muhammed Amir Essibayi,Amanda Baker,David Altschul,Luca Scarcia,Erwah Kalsoum,Adam A Dmytriw,Adrien Guenego,MAD-MT Consortium

Source: Clinical neuroradiology

CONCLUSION: Anaesthetic strategy in MeVOs does not influence favorable outcomes or final successful recanalization rates, however, GA may be associated with an increased risk of sICH and mortality.

Neuropsychiatric complications of coronavirus disease 2019: Mount Sinai Health System cohort study

miércoles, abril 24, 2024

Author(s): Kapil Gururangan,Veronica J Peschansky,Grace Van Hyfte,Parul Agarwal,Leah J Blank,Brian Mathew,Jonathan Goldstein,Churl-Su Kwon,Louise McCarthy,Ariella Cohen,Andy Ho Wing Chan,Pojen Deng,Mandip Dhamoon,Eveline Gutzwiller,Qing Hao,Celestine He,Britany Klenofsky,Hernan Nicolas Lemus,Lara Marcuse,Allison Navis,Wilson D Heredia Nunez,Mallory N Luckey,Emily M Schorr,Anuradha Singh,Gabriela B Tantillo,Claire Ufongene,James J Young,Priti Balchandani,Joanne R Festa,Georges Naasan,Alexander W Charney,Girish N Nadkarni,Nathalie Jetté,Sinai NeuroCOVID-19 Study Group

Source: Journal of neurology

CONCLUSION: Neuropsychiatric complications of COVID-19, especially AMS, were common, varied, and associated with in-hospital mortality in a diverse multicenter cohort at an epicenter of the COVID-19 pandemic.

Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial

miércoles, abril 17, 2024

Author(s): Rabi Tawil,Kathryn R Wagner,Johanna I Hamel,Doris G Leung,Jeffrey M Statland,Leo H Wang,Angela Genge,Sabrina Sacconi,Hanns Lochmüller,David Reyes-Leiva,Jordi Diaz-Manera,Jorge Alonso-Perez,Nuria Muelas,Juan J Vilchez,Alan Pestronk,Summer Gibson,Namita A Goyal,Lawrence J Hayward,Nicholas Johnson,Samantha LoRusso,Miriam Freimer,Perry B Shieh,S H Subramony,Baziel van Engelen,Joost Kools,Olof Dahlqvist Leinhard,Per Widholm,Christopher Morabito,Christopher M Moxham,Diego Cadavid,Michelle L Mellion,Adefowope Odueyungbo,William G Tracewell,Anthony Accorsi,Lucienne Ronco,Robert J Gould,Jennifer Shoskes,Luis Alejandro Rojas,John G Jiang

Source: The Lancet. Neurology

BACKGROUND: Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38α MAPK, a regulator of DUX4 expression, and p38β MAPK) for the treatment of facioscapulohumeral muscular dystrophy.

Multiple sclerosis can be diagnosed solely with dissemination in space: No

lunes, abril 15, 2024

Author(s): Christopher C Hemond,Andrew J Solomon

Source: Multiple sclerosis (Houndmills, Basingstoke, England)

No abstract

External validation of the SI2NCAL2C score for outcomes following cerebral venous thrombosis

sábado, abril 13, 2024

Author(s): Piers Klein,Liqi Shu,Erik Lindgren,Maria A de Winter,James E Siegler,Alexis N Simpkins,Satareh Salehi Omran,Mirjam R Heldner,Adam de Havenon,Mohamad Abdalkader,Sami Al Kasab,Christoph Stretz,Teddy Y Wu,Duncan Wilson,Syed Daniyal Asad,Eyad Almallouhi,Jennifer Frontera,Lindsey Kuohn,Aaron Rothstein,Ekaterina Bakradze,Nils Henninger,Adeel S Zubair,Richa Sharma,Deborah Kerrigan,Yasmin Aziz,Eva A Mistry,Mayte Sanchez van Kammen,Turgut Tatlisumak,Katarzyna Krzywicka,Diana Aguiar de Sousa,Katarina Jood,Thalia S Field,Shadi Yaghi,Jonathan M Coutinho,Thanh N Nguyen

Source: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association

CONCLUSIONS: The SI(2)NCAL(2)C score had acceptable to good performance in an international external validation cohort. The SI(2)NCAL(2)C score warrants additional validation studies in diverse populations and clinical implementation studies.

Debamestrocel multimodal effects on biomarker pathways in amyotrophic lateral sclerosis are linked to clinical outcomes

martes, abril 09, 2024

Author(s): Stacy R Lindborg,Namita A Goyal,Jonathan Katz,Matthew Burford,Jenny Li,Haggai Kaspi,Natalie Abramov,Bruno Boulanger,James D Berry,Katharine Nicholson,Tahseen Mozaffar,Robert Miller,Liberty Jenkins,Robert H Baloh,Richard Lewis,Nathan P Staff,Margaret Ayo Owegi,Bob Dagher,Netta R Blondheim-Shraga,Yael Gothelf,Yossef S Levy,Ralph Kern,Revital Aricha,Anthony J Windebank,Robert Bowser,Robert H Brown,Merit E Cudkowicz

Source: Muscle & nerve

INTRODUCTION/AIMS: Biomarkers have shown promise in amyotrophic lateral sclerosis (ALS) research, but the quest for reliable biomarkers remains active. This study evaluates the effect of debamestrocel on cerebrospinal fluid (CSF) biomarkers, an exploratory endpoint.

Traumatic injury causes selective degeneration and TDP-43 mislocalization in human iPSC-derived C9orf72-associated ALS/FTD motor neurons

lunes, abril 08, 2024

Author(s): Eric J Martin,Citlally Santacruz,Angela Mitevska,Ian E Jones,Gopinath Krishnan,Fen-Biao Gao,John D Finan,Evangelos Kiskinis

Source: bioRxiv : the preprint server for biology

A hexanucleotide repeat expansion (HRE) in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, patients with the HRE exhibit a wide disparity in clinical presentation and age of symptom onset suggesting an interplay between genetic background and environmental stressors. Neurotrauma as a result of traumatic brain or spinal cord injury has been shown to increase the risk of ALS/FTD in epidemiological studies. Here, we combine...

Exceptionally long-lived nuclear RNAs

jueves, abril 04, 2024

Author(s): Jeanne Lawrence,Lisa Hall

Source: Science (New York, N.Y.)

RNA labeled in young mice is detected 2 years later in adult mouse brains.

Expression of ALS-PFN1 impairs vesicular degradation in iPSC-derived microglia

jueves, marzo 21, 2024

Author(s): Salome Funes,Jonathan Jung,Del Hayden Gadd,Michelle Mosqueda,Jianjun Zhong,None Shankaracharya,Matthew Unger,Karly Stallworth,Debra Cameron,Melissa S Rotunno,Pepper Dawes,Megan Fowler-Magaw,Pamela J Keagle,Justin A McDonough,Sivakumar Boopathy,Miguel Sena-Esteves,Jeffrey A Nickerson,Cathleen Lutz,William C Skarnes,Elaine T Lim,Dorothy P Schafer,Francesca Massi,John E Landers,Daryl A Bosco

Source: Nature communications

Microglia play a pivotal role in neurodegenerative disease pathogenesis, but the mechanisms underlying microglia dysfunction and toxicity remain to be elucidated. To investigate the effect of neurodegenerative disease-linked genes on the intrinsic properties of microglia, we studied microglia-like cells derived from human induced pluripotent stem cells (iPSCs), termed iMGs, harboring mutations in profilin-1 (PFN1) that are causative for amyotrophic lateral sclerosis (ALS). ALS-PFN1 iMGs...

Feasibility study of microburst VNS therapy in drug-resistant focal and generalized epilepsy

lunes, marzo 18, 2024

Author(s): Cornelia Drees,Pegah Afra,Ryan Verner,Lesley Kaye,Amy Keith,Mei Jiang,Jerzy P Szaflarski,Kathryn Nichol,Microburst Study Group

Source: Brain stimulation

CONCLUSION: Overall, μVNS appears to be safe and potentially a promising therapeutic alternative to traditional VNS. It merits further investigation in randomized controlled trials which will help determine the impact of investigational variables and which patients are most suitable for this novel therapy.

Machine Learning and Digital Biomarkers Can Detect Early Stages of Neurodegenerative Diseases

miércoles, marzo 13, 2024

Author(s): Artur Chudzik,Albert Śledzianowski,Andrzej W Przybyszewski

Source: Sensors (Basel, Switzerland)

Neurodegenerative diseases (NDs) such as Alzheimer's Disease (AD) and Parkinson's Disease (PD) are devastating conditions that can develop without noticeable symptoms, causing irreversible damage to neurons before any signs become clinically evident. NDs are a major cause of disability and mortality worldwide. Currently, there are no cures or treatments to halt their progression. Therefore, the development of early detection methods is urgently needed to delay neuronal loss as soon as possible....

Emerging Cerebrospinal Fluid Biomarkers of Disease Activity and Progression in Multiple Sclerosis

lunes, marzo 11, 2024

Author(s): Anne H Cross,Jeffrey M Gelfand,Simon Thebault,Jeffrey L Bennett,H Christian von Büdingen,Briana Cameron,Robert Carruthers,Keith Edwards,Robert Fallis,Rachel Gerstein,Paul S Giacomini,Benjamin Greenberg,David A Hafler,Carolina Ionete,Ulrike W Kaunzner,Lay Kodama,Christopher Lock,Erin E Longbrake,Bruno Musch,Gabriel Pardo,Fredrik Piehl,Martin S Weber,Steven Yuen,Tjalf Ziemssen,Gauruv Bose,Mark S Freedman,Veronica G Anania,Akshaya Ramesh,Ryan C Winger,Xiaoming Jia,Ann Herman,Christopher Harp,Amit Bar-Or

Source: JAMA neurology

CONCLUSIONS AND RELEVANCE: In this study, activated glial markers (in particular GFAP) and neurofilament heavy chain were associated specifically with nonrelapsing progressive disease outcomes (independent of acute inflammatory activity). Elevated CSF GFAP was associated with long-term MS disease progression.

Trisomy silencing by XIST: translational prospects and challenges

viernes, marzo 08, 2024

Author(s): Khusali Gupta,Jan T Czerminski,Jeanne B Lawrence

Source: Human genetics

XIST RNA is heavily studied for its role in fundamental epigenetics and X-chromosome inactivation; however, the translational potential of this singular RNA has been much less explored. This article combines elements of a review on XIST biology with our perspective on the translational prospects and challenges of XIST transgenics. We first briefly review aspects of XIST RNA basic biology that are key to its translational relevance, and then discuss recent efforts to develop translational utility...

Incidence and clinical outcomes of perforations during mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke: A retrospective, multicenter, and multinational study

martes, febrero 27, 2024

Author(s): Adam A Dmytriw,Basel Musmar,Hamza Salim,Sherief Ghozy,James E Siegler,Hassan Kobeissi,Hamza Shaikh,Jane Khalife,Mohamad Abdalkader,Piers Klein,Thanh N Nguyen,Jeremy J Heit,Robert W Regenhardt,Nicole M Cancelliere,Joshua D Bernstock,Kareem El Naamani,Abdelaziz Amllay,Lukas Meyer,Anne Dusart,Flavio Bellante,Géraud Forestier,Aymeric Rouchaud,Suzana Saleme,Charbel Mounayer,Jens Fiehler,Anna Luisa Kühn,Ajit S Puri,Christian Dyzmann,Peter T Kan,Marco Colasurdo,Gaultier Marnat,Jérôme Berge,Xavier Barreau,Igor Sibon,Simona Nedelcu,Nils Henninger,Thomas R Marotta,Christopher J Stapleton,James D Rabinov,Takahiro Ota,Shogo Dofuku,Leonard Ll Yeo,Benjamin Yq Tan,Anil Gopinathan,Juan Carlos Martinez-Gutierrez,Sergio Salazar-Marioni,Sunil Sheth,Leonardo Renieri,Carolina Capirossi,Ashkan Mowla,Lina Chervak,Achala Vagal,Nimer Adeeb,Hugo H Cuellar-Saenz,Stavropoula I Tjoumakaris,Pascal Jabbour,Priyank Khandelwal,Arundhati Biswas,Frédéric Clarençon,Mahmoud Elhorany,Kevin Premat,Iacopo Valente,Alessandro Pedicelli,João Pedro Filipe,Ricardo Varela,Miguel Quintero-Consuegra,Nestor R Gonzalez,Markus A Möhlenbruch,Jessica Jesser,Vincent Costalat,Adrien Ter Schiphorst,Vivek Yedavalli,Pablo Harker,Yasmin Aziz,Benjamin Gory,Christian Paul Stracke,Constantin Hecker,Ramanathan Kadirvel,Monika Killer-Oberpfalzer,Christoph J Griessenauer,Ajith J Thomas,Cheng-Yang Hsieh,David S Liebeskind,Răzvan Alexandru Radu,Andrea M Alexandre,Illario Tancredi,Tobias D Faizy,Robert Fahed,Charlotte Weyland,Boris Lubicz,Aman B Patel,Vitor Mendes Pereira,Adrien Guenego,MAD-MT Consortium

Source: European stroke journal

CONCLUSION: This study reveals that while the occurrence of vessel perforation in MT for AIS due to MeVO is relatively rare, it is associated with poor functional outcomes and higher mortality. The findings highlight the need for increased caution and specialized training in performing MT for MeVO. Further prospective research is required for risk mitigation strategies.

Evaluating the Clinical Utility of Epstein-Barr Virus Antibodies as Biomarkers in Multiple Sclerosis: A Systematic Review

sábado, febrero 24, 2024

Author(s): Abigail Bose,Farnaz Khalighinejad,David C Hoaglin,Christopher C Hemond

Source: Multiple sclerosis and related disorders

CONCLUSION: Heterogeneous methodology limited generalization and meta-analysis. EBV antibody levels are unlikely to represent prognostic biomarkers in MS. The areas of highest ongoing promise relate to diagnostic exclusion and pharmacodynamic/disease response. Use of EBV antibodies as biomarkers in clinical practice remains additionally limited by lack of methodological precision, reliability, and validation.

Chemotherapy-associated hemorrhagic posterior reversible encephalopathy syndrome (PRES) with considerations for circle of Willis variants on cerebral blood flow and autoregulation: A case report

viernes, febrero 23, 2024

Author(s): Bahadar S Srichawla,Kendall Presti,Vincent Kipkorir,Idanis Berrios Morales

Source: Medicine

RATIONALE: Hodgkin lymphoma, a lymphatic system cancer, is treated by chemotherapy, radiation therapy, and hematopoietic stem cell transplantation. Posterior reversible encephalopathy syndrome (PRES) is a rare neurotoxic effect associated with several drugs and systemic conditions. This case study emphasizes the potential risks of intensive chemotherapy regimens and postulates the impact of the circle of Willis variants on the heterogeneity of hemispheric lesions in PRES.

A Paradox of the Field's Own Success: Unintended Challenges in Bringing Cutting-Edge Science from the Bench to the Market

miércoles, febrero 21, 2024

Author(s): Nathan Yingling,Miguel Sena-Esteves,Heather L Gray-Edwards

Source: Human gene therapy

No abstract

Use of the pRESET LITE thrombectomy device in combined approach for medium vessel occlusions: A multicenter evaluation

miércoles, febrero 21, 2024

Author(s): Maud Wang,Hans Henkes,Sherief Ghozy,James E Siegler,Hamza Shaikh,Jane Khalife,Mohamad Abdalkader,Piers Klein,Thanh N Nguyen,Jeremy J Heit,Ahmad Sweid,Kareem El Naamani,Robert W Regenhardt,Jose Danilo Bengzon Diestro,Nicole M Cancelliere,Abdelaziz Amllay,Lukas Meyer,Anne Dusart,Flavio Bellante,Géraud Forestier,Aymeric Rouchaud,Suzana Saleme,Charbel Mounayer,Jens Fiehler,Anna Luisa Kühn,Ajit S Puri,Christian Dyzmann,Peter T Kan,Marco Colasurdo,Gaultier Marnat,Jérôme Berge,Xavier Barreau,Igor Sibon,Simona Nedelcu,Nils Henninger,Charlotte Weyland,Thomas R Marotta,Christopher J Stapleton,James D Rabinov,Takahiro Ota,Shogo Dofuku,Leonard Ll Yeo,Benjamin Y Q Tan,Juan Carlos Martinez-Gutierrez,Sergio Salazar-Marioni,Sunil Sheth,Leonardo Renieri,Carolina Capirossi,Ashkan Mowla,Stavropoula I Tjoumakaris,Pascal Jabbour,Priyank Khandelwal,Arundhati Biswas,Frédéric Clarençon,Mahmoud Elhorany,Kevin Premat,Iacopo Valente,Alessandro Pedicelli,João Pedro Filipe,Ricardo Varela,Miguel Quintero-Consuegra,Nestor R Gonzalez,Markus A Möhlenbruch,Jessica Jesser,Vincent Costalat,Adrien Ter Schiphorst,Vivek Yedavalli,Pablo Harker,Lina M Chervak,Yasmin Aziz,Benjamin Gory,Christian Paul Stracke,Constantin Hecker,Monika Killer-Oberpfalzer,Christoph J Griessenauer,Ajith J Thomas,Cheng-Yang Hsieh,David S Liebeskind,Răzvan Alexandru Radu,Andrea M Alexandre,Illario Tancredi,Tobias D Faizy,Aman B Patel,Vitor Mendes Pereira,Robert Fahed,Boris Lubicz,Adam A Dmytriw,Adrien Guenego,M.A.D.-M.T. Consortium

Source: Neuroradiology

CONCLUSION: Mechanical thrombectomy using the pRESET LITE in a combined approach with an aspiration catheter appears effective for primary medium vessel occlusions across several centers and physicians.

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study

viernes, febrero 09, 2024

Author(s): Shadi Yaghi,Liqi Shu,Daniel Mandel,Christopher R Leon Guerrero,Nils Henninger,Jayachandra Muppa,Muhammad Affan,Omair Ul Haq Lodhi,Mirjam R Heldner,Kateryna Antonenko,David Seiffge,Marcel Arnold,Setareh Salehi Omran,Ross Crandall,Evan Lester,Diego Lopez Mena,Antonio Arauz,Ahmad Nehme,Marion Boulanger,Emmanuel Touze,Joao Andre Sousa,Joao Sargento-Freitas,Vasco Barata,Paulo Castro-Chaves,Maria Teresa Brito,Muhib Khan,Dania Mallick,Aaron Rothstein,Ossama Khazaal,Josefin E Kaufmann,Stefan T Engelter,Christopher Traenka,Diana Aguiar de Sousa,Mafalda Soares,Sara Rosa,Lily W Zhou,Preet Gandhi,Thalia S Field,Steven Mancini,Issa Metanis,Ronen R Leker,Kelly Pan,Vishnu Dantu,Karl Baumgartner,Tina Burton,Regina Von Rennenberg,Christian H Nolte,Richard Choi,Jason MacDonald,Reza Bavarsad Shahripour,Xiaofan Guo,Malik Ghannam,Mohammad Almajali,Edgar A Samaniego,Sebastian Sanchez,Bastien Rioux,Faycal Zine-Eddine,Alexandre Poppe,Ana Catarina Fonseca,Maria Fortuna Baptista,Diana Cruz,Michele Romoli,Giovanna De Marco,Marco Longoni,Zafer Keser,Kim Griffin,Lindsey Kuohn,Jennifer Frontera,Jordan Amar,James Giles,Marialuisa Zedde,Rosario Pascarella,Ilaria Grisendi,Hipolito Nzwalo,David S Liebeskind,Amir Molaie,Annie Cavalier,Wayneho Kam,Brian Mac Grory,Sami Al Kasab,Mohammad Anadani,Kimberly Kicielinski,Ali Eltatawy,Lina Chervak,Roberto Chulluncuy-Rivas,Yasmin Aziz,Ekaterina Bakradze,Thanh Lam Tran,Marc Rodrigo-Gisbert,Manuel Requena,Faddi Saleh Velez,Jorge Ortiz Gracia,Varsha Mudassani,Adam de Havenon,Venugopalan Y Vishnu,Sridhara Yaddanapudi,Latasha Adams,Abigail Browngoehl,Tamra Ranasinghe,Randy Dunston,Zachary Lynch,Mary Penckofer,James Siegler,Silvia Mayer,Joshua Willey,Adeel Zubair,Yee Kuang Cheng,Richa Sharma,João Pedro Marto,Vítor Mendes Ferreira,Piers Klein,Thanh N Nguyen,Syed Daniyal Asad,Zoha Sarwat,Anvesh Balabhadra,Shivam Patel,Thais Secchi,Sheila Martins,Gabriel Mantovani,Young Dae Kim,Balaji Krishnaiah,Cheran Elangovan,Sivani Lingam,Abid Quereshi,Sebastian Fridman,Alonso Alvarado,Farid Khasiyev,Guillermo Linares,Marina Mannino,Valeria Terruso,Sofia Vassilopoulou,Vasilis Tentolouris,Manuel Martinez-Marino,Victor Carrasco Wall,Fransisca Indraswari,Sleiman El Jamal,Shilin Liu,Muhammad Alvi,Farman Ali,Mohammed Sarvath,Rami Z Morsi,Tareq Kass-Hout,Feina Shi,Jinhua Zhang,Dilraj Sokhi,Jamil Said,Alexis N Simpkins,Roberto Gomez,Shayak Sen,Mohammad Ghani,Marwa Elnazeir,Han Xiao,Narendra Kala,Farhan Khan,Christoph Stretz,Nahid Mohammadzadeh,Eric Goldstein,Karen Furie

Source: Stroke

CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Inorganic polyphosphate: from basic research to diagnostic and therapeutic opportunities in ALS/FTD

miércoles, febrero 07, 2024

Author(s): Polett Garcés,Armando Amaro,Martin Montecino,Brigitte van Zundert

Source: Biochemical Society transactions

Inorganic polyphosphate (polyP) is a simple, negatively charged biopolymer with chain lengths ranging from just a few to over a thousand ortho-phosphate (Pi) residues. polyP is detected in every cell type across all organisms in nature thus far analyzed. Despite its structural simplicity, polyP has been shown to play important roles in a remarkably broad spectrum of biological processes, including blood coagulation, bone mineralization and inflammation. Furthermore, polyP has been implicated in...

Transcarotid Arterial Revascularization of Symptomatic Internal Carotid Artery Disease: A Systematic Review and Study-Level Meta-Analysis

jueves, febrero 01, 2024

Author(s): Malik Ghannam,Mohammad AlMajali,Farid Khasiyev,Mahmoud Dibas,Abdullah Al Qudah,Fawaz AlMajali,Dana Ghazaleh,Asghar Shah,Fayez H Fayad,Kareem Joudi,Bashar Zaidat,Christopher A Childs,Bennett R Levy,Yasmeen Abouainain,Denise M D Özdemir-van Brunschot,Liqi Shu,Eric D Goldstein,Ammad A Baig,Hannah Roeder,Nils Henninger,Adam de Havenon,Elad I Levy,Charles Matouk,Colin P Derdeyn,Enrique C Leira,Seemant Chaturvedi,Shadi Yaghi

Source: Stroke

CONCLUSIONS: Although CEA has traditionally been considered superior to stenting for symptomatic carotid stenosis, TCAR may have some advantages over CAS. Prospective randomized trials comparing the 3 modalities are needed.

Evaluating protein cross-linking as a therapeutic strategy to stabilize SOD1 variants in a mouse model of familial ALS

martes, enero 30, 2024

Author(s): Md Amin Hossain,Richa Sarin,Daniel P Donnelly,Brandon C Miller,Alexandra Weiss,Luke McAlary,Svetlana V Antonyuk,Joseph P Salisbury,Jakal Amin,Jeremy B Conway,Samantha S Watson,Jenifer N Winters,Yu Xu,Novera Alam,Rutali R Brahme,Haneyeh Shahbazian,Durgalakshmi Sivasankar,Swathi Padmakumar,Aziza Sattarova,Aparna C Ponmudiyan,Tanvi Gawde,David E Verrill,Wensheng Yang,Sunanda Kannapadi,Leigh D Plant,Jared R Auclair,Lee Makowski,Gregory A Petsko,Dagmar Ringe,Nathalie Y R Agar,David J Greenblatt,Mary Jo Ondrechen,Yunqiu Chen,Justin J Yerbury,Roman Manetsch,S Samar Hasnain,Robert H Brown,Jeffrey N Agar

Source: PLoS biology

Mutations in the gene encoding Cu-Zn superoxide dismutase 1 (SOD1) cause a subset of familial amyotrophic lateral sclerosis (fALS) cases. A shared effect of these mutations is that SOD1, which is normally a stable dimer, dissociates into toxic monomers that seed toxic aggregates. Considerable research effort has been devoted to developing compounds that stabilize the dimer of fALS SOD1 variants, but unfortunately, this has not yet resulted in a treatment. We hypothesized that cyclic...

Characterization of cortico-meningeal translocator protein expression in multiple sclerosis

martes, enero 30, 2024

Author(s): Elena Herranz,Constantina A Treaba,Valeria T Barletta,Ambica Mehndiratta,Russell Ouellette,Jacob A Sloane,Carolina Ionete,Suma Babu,Marina Mastantuono,Stefano Magon,Marco L Loggia,Meena M Makary,Jacob M Hooker,Ciprian Catana,Revere Kinkel,Richard Nicholas,Eric C Klawiter,Roberta Magliozzi,Caterina Mainero

Source: Brain : a journal of neurology

Compartmentalized meningeal inflammation is thought to represent one of the key players in the pathogenesis of cortical demyelination in multiple sclerosis. Positron emission tomography targeting the 18 kDa mitochondrial Translocator Protein (TSPO) is a molecular-specific approach to quantify immune cell-mediated density in the cortico-meningeal tissue compartment in vivo. The aim of this study was to characterize cortical and meningeal TSPO expression in a heterogeneous cohort of multiple...

Differences in Alu vs L1-rich chromosome bands underpin architectural reorganization of the inactive-X chromosome and SAHFs

martes, enero 23, 2024

Author(s): Lisa L Hall,Kevin M Creamer,Meg Byron,Jeanne B Lawrence

Source: bioRxiv : the preprint server for biology

The linear DNA sequence of mammalian chromosomes is organized in large blocks of DNA with similar sequence properties, producing a pattern of dark and light staining bands on mitotic chromosomes. Cytogenetic banding is essentially invariant between people and cell-types and thus may be assumed unrelated to genome regulation. We investigate whether large blocks of Alu-rich R-bands and L1-rich G-bands provide a framework upon which functional genome architecture is built. We examine two models of...

PAD2 dysregulation and aberrant protein citrullination feature prominently in reactive astrogliosis and myelin protein aggregation in sporadic ALS

lunes, enero 22, 2024

Author(s): Issa O Yusuf,Sepideh Parsi,Lyle W Ostrow,Robert H Brown,Paul R Thompson,Zuoshang Xu

Source: Neurobiology of disease

Alteration in protein citrullination (PC), a common posttranslational modification (PTM), contributes to pathogenesis in various inflammatory disorders. We previously reported that PC and protein arginine deiminase 2 (PAD2), the predominant enzyme isoform that catalyzes this PTM in the central nervous system (CNS), are altered in mouse models of amyotrophic lateral sclerosis (ALS). We now demonstrate that PAD2 expression and PC are altered in human postmortem ALS spinal cord and motor cortex...

Is catheter ablation associated with preservation of cognitive function? An analysis from the SAGE-AF observational cohort study

lunes, enero 22, 2024

Author(s): Bahadar S Srichawla,Alexander P Hamel,Philip Cook,Rozaleen Aleyadeh,Darleen Lessard,Edith M Otabil,Jordy Mehawej,Jane S Saczynski,David D McManus,Majaz Moonis

Source: Frontiers in neurology

CONCLUSION: In this 2-year longitudinal prospective cohort study participants who underwent CA for AF before enrollment were less likely to have cognitive impairment than those who had not undergone CA.

Imaging chronic active lesions in multiple sclerosis: a consensus statement

martes, enero 16, 2024

Author(s): Francesca Bagnato,Pascal Sati,Christopher C Hemond,Colm Elliott,Susan A Gauthier,Daniel M Harrison,Caterina Mainero,Jiwon Oh,David Pitt,Russell T Shinohara,Seth A Smith,Bruce Trapp,Christina J Azevedo,Peter A Calabresi,Roland G Henry,Cornelia Laule,Daniel Ontaneda,William D Rooney,Nancy L Sicotte,Daniel S Reich,Martina Absinta

Source: Brain : a journal of neurology

Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis (MS) and have implications for non-relapsing biological progression. In recent years, the discovery of innovative magnetic resonance imaging (MRI) and PET derived biomarkers has made it possible to detect CAL, and to some extent quantify them, in the brain of persons with MS, in vivo. Paramagnetic rim lesions on susceptibility-sensitive MRI sequences, MRI-defined slowly expanding lesions on...

The Clinical Development of Taldefgrobep Alfa: An Anti-Myostatin Adnectin for the Treatment of Duchenne Muscular Dystrophy

lunes, enero 08, 2024

Author(s): Francesco Muntoni,Barry J Byrne,Hugh J McMillan,Monique M Ryan,Brenda L Wong,Juergen Dukart,Amita Bansal,Valerie Cosson,Roxana Dreghici,Maitea Guridi,Michael Rabbia,Hannah Staunton,Giridhar S Tirucherai,Karl Yen,Xiling Yuan,Kathryn R Wagner,Taldefgrobep Alfa Study Group

Source: Neurology and therapy

CONCLUSIONS: The futility analysis demonstrated that taldefgrobep alfa did not result in functional change for boys with DMD. The program was subsequently terminated in 2019. Overall, there were no safety concerns, and no patients were withdrawn from treatment as a result of treatment-related adverse events or serious adverse events.

Genetic ablation of Sarm1 attenuates expression and mislocalization of phosphorylated TDP-43 after mouse repetitive traumatic brain injury

jueves, diciembre 21, 2023

Author(s): Elif O Dogan,James Bouley,Jianjun Zhong,Ashley L Harkins,Allison M Keeler,Daryl A Bosco,Robert H Brown,Nils Henninger

Source: Acta neuropathologica communications

Traumatic brain injury (TBI), particularly when moderate-to-severe and repetitive, is a strong environmental risk factor for several progressive neurodegenerative disorders. Mislocalization and deposition of transactive response DNA binding protein 43 (TDP-43) has been reported in both TBI and TBI-associated neurodegenerative diseases. It has been hypothesized that axonal pathology, an early event after TBI, may promote TDP-43 dysregulation and serve as a trigger for neurodegenerative processes....

Endovascular therapy versus medical management for mild strokes due to medium and distal vessel occlusions

lunes, diciembre 18, 2023

Author(s): Simona Nedelcu,Akanksha Gulati,Nils Henninger

Source: Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences

CONCLUSIONS: We found that among DMVO patients with low admission NIHSS treatment with EVT versus BMT was associated with similar outcomes. Larger prospective studies are required to confirm these findings.

Is Catheter Ablation Associated with Preservation of Cognitive Function? An Analysis From the SAGE-AF Observational Cohort Study

lunes, diciembre 04, 2023

Author(s): Bahadar S Srichawla,Alexander P Hamel,Philip Cook,Rozaleen Aleyadeh,Darleen Lessard,Edith M Otabil,Jordy Mehawej,Jane S Saczynski,David D McManus,Majaz Moonis

Source: medRxiv : the preprint server for health sciences

CONCLUSIONS: In this two-year longitudinal prospective cohort study participants who underwent CA for AF before enrollment were less likely to have cognitive impairment than those who had not undergone CA.

An Adjustable Magnetic Levator Prosthesis for Customizable Eyelid Reanimation in Severe Blepharoptosis II: Randomized Evaluation of Angular Translation

viernes, diciembre 01, 2023

Author(s): Pooyan Tirandazi,Melanie Nadeau,Russell L Woods,Eleftherios I Paschalis,Kevin E Houston

Source: Translational vision science & technology

CONCLUSIONS: Angular translation provided adjustable force, which had a statistically and clinically meaningful impact on eye opening and the completeness of the spontaneous blink. This quantitative evidence supports continued use of the angular translation mechanism for force adjustment in the customizable magnetic correction of severe blepharoptosis.

Cyclonite-Induced Seizures After Voluntary C-4 Ingestion

miércoles, noviembre 29, 2023

Author(s): Ton Fang,Paramesh V Karandikar,Taylor R Young,Raffaella P Umeton

Source: Cureus

Cyclonite (cyclotrimethylenetrinitramine, RDX, hexogen) is the active agent in the plastic explosive, composition 4 (C-4). It has been used globally since the Vietnam War for both military and civilian applications due to its metastable nature. Ingestion or inhalation of C-4 can cause euphoric effects such as those commonly seen with alcohol toxicity, in addition to seizures and rarely fulminant liver and kidney failure. We report the case of a patient who ingested 75 g of C-4 and presented with...

WarpDrive: Improving spatial normalization using manual refinements

domingo, noviembre 26, 2023

Author(s): Simón Oxenford,Ana Sofía Ríos,Barbara Hollunder,Clemens Neudorfer,Alexandre Boutet,Gavin J B Elias,Jurgen Germann,Aaron Loh,Wissam Deeb,Bryan Salvato,Leonardo Almeida,Kelly D Foote,Robert Amaral,Paul B Rosenberg,David F Tang-Wai,David A Wolk,Anna D Burke,Marwan N Sabbagh,Stephen Salloway,M Mallar Chakravarty,Gwenn S Smith,Constantine G Lyketsos,Michael S Okun,William S Anderson,Zoltan Mari,Francisco A Ponce,Andres Lozano,Wolf-Julian Neumann,Bassam Al-Fatly,Andreas Horn

Source: Medical image analysis

Spatial normalization-the process of mapping subject brain images to an average template brain-has evolved over the last 20+ years into a reliable method that facilitates the comparison of brain imaging results across patients, centers & modalities. While overall successful, sometimes, this automatic process yields suboptimal results, especially when dealing with brains with extensive neurodegeneration and atrophy patterns, or when high accuracy in specific regions is needed. Here we introduce...

c-Abl Phosphorylates MFN2 to Regulate Mitochondrial Morphology in Cells under Endoplasmic Reticulum and Oxidative Stress, Impacting Cell Survival and Neurodegeneration

sábado, noviembre 25, 2023

Author(s): Alexis Martinez,Cristian M Lamaizon,Cristian Valls,Fabien Llambi,Nancy Leal,Patrick Fitzgerald,Cliff Guy,Marcin M Kamiński,Nibaldo C Inestrosa,Brigitte van Zundert,Gonzalo I Cancino,Andrés E Dulcey,Silvana Zanlungo,Juan J Marugan,Claudio Hetz,Douglas R Green,Alejandra R Alvarez

Source: Antioxidants (Basel, Switzerland)

The endoplasmic reticulum is a subcellular organelle key in the control of synthesis, folding, and sorting of proteins. Under endoplasmic reticulum stress, an adaptative unfolded protein response is activated; however, if this activation is prolonged, cells can undergo cell death, in part due to oxidative stress and mitochondrial fragmentation. Here, we report that endoplasmic reticulum stress activates c-Abl tyrosine kinase, inducing its translocation to mitochondria. We found that endoplasmic...

Gaze Scanning at Street Crossings by Pedestrians With Homonymous Hemianopia With and Without Hemispatial Neglect

viernes, noviembre 17, 2023

Author(s): Shrinivas Pundlik,Matteo Tomasi,Kevin E Houston,Ayush Kumar,Prerana Shivshanker,Alex R Bowers,Eli Peli,Gang Luo

Source: Investigative ophthalmology & visual science

CONCLUSIONS: All groups demonstrated compensatory scanning, making more gaze scans with larger magnitudes to the blind side. Mild to moderate LHSN adversely impacted the scanning rate.

Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism

jueves, noviembre 16, 2023

Author(s): Justin Cohen,Shushu Huang,Katherine E Koczwara,Kristen T Woods,Vincent Ho,Keryn G Woodman,Jack L Arbiser,Katelyn Daman,Monkol Lek,Charles P Emerson,Alec M DeSimone

Source: Cell death & disease

Facioscapulohumeral muscular dystrophy (FSHD) is among the most common of the muscular dystrophies, affecting nearly 1 in 8000 individuals, and is a cause of profound disability. Genetically, FSHD is linked to the contraction and/or epigenetic de-repression of the D4Z4 repeat array on chromosome 4, thereby allowing expression of the DUX4 gene in skeletal muscle. If the DUX4 transcript incorporates a stabilizing polyadenylation site the myotoxic DUX4 protein will be synthesized, resulting in...

Guidelines for neuroprognostication in adults with traumatic spinal cord injury

lunes, noviembre 13, 2023

Author(s): Dea Mahanes,Susanne Muehlschlegel,Katja E Wartenberg,Venkatakrishna Rajajee,Sheila A Alexander,Katharina M Busl,Claire J Creutzfeldt,Gabriel V Fontaine,Sara E Hocker,David Y Hwang,Keri S Kim,Dominik Madzar,Shraddha Mainali,Juergen Meixensberger,Panayiotis N Varelas,Christian Weimar,Thomas Westermaier,Oliver W Sakowitz

Source: Neurocritical care

CONCLUSIONS: These guidelines provide recommendations about the reliability of acute-phase predictors of mortality, functional outcome, American Spinal Injury Association Impairment Scale grade conversion, and recovery of independent ambulation for consideration when counseling patients with tSCI or their surrogates and suggest broad principles of neuroprognostication in this context.

Implementing Shared Decision-Making for Multiple Sclerosis: The MS-SUPPORT Tool

lunes, noviembre 06, 2023

Author(s): Nananda F Col,Andrew J Solomon,Enrique Alvarez,Lori Pbert,Carolina Ionete,Idanis BerriosMorales,Jennifer Chester,Christen Kutz,Crystal Iwuchukwu,Terrie Livingston,Vicky Springmann,Hannah V Col,Long H Ngo

Source: Multiple sclerosis and related disorders

CONCLUSIONS: MS-SUPPORT was strongly endorsed by patients and is feasible to use in clinical settings. MS-SUPPORT increased the short-term probability of taking and adhering to a DMT, and improved long-term mental health. Study limitations include selection bias, response bias, social desirability bias, and recall bias. Exploring approaches to reinforcement and monitoring its implementation in real-world settings should provide further insights into the value and utility of this new SDM tool.

A Targeted Approach for Evaluating DUX4-Regulated Proteins as Potential Serum Biomarkers for Facioscapulohumeral Muscular Dystrophy Using Immunoassay Proteomics

domingo, octubre 29, 2023

Author(s): Amy E Campbell,Jamshid Arjomand,Oliver D King,Rabi Tawil,Sujatha Jagannathan

Source: Journal of neuromuscular diseases

CONCLUSIONS: ALPP, as measured with the Olink Proteomics platform, is not a promising FSHD serum biomarker candidate but could be utilized to evaluate DUX4 activity in discovery research efforts.

First pass effect as an independent predictor of functional outcomes in medium vessel occlusions: An analysis of an international multicenter study

viernes, octubre 27, 2023

Author(s): Răzvan Alexandru Radu,Vincent Costalat,Robert Fahed,Sherief Ghozy,James E Siegler,Hamza Shaikh,Jane Khalife,Mohamad Abdalkader,Piers Klein,Thanh N Nguyen,Jeremy J Heit,Ahmad Sweid,Kareem El Naamani,Robert W Regenhardt,Jose Danilo Bengzon Diestro,Nicole M Cancelliere,Abdelaziz Amllay,Lukas Meyer,Anne Dusart,Flavio Bellante,Géraud Forestier,Aymeric Rouchaud,Suzana Saleme,Charbel Mounayer,Jens Fiehler,Anna Luisa Kühn,Ajit S Puri,Christian Dyzmann,Peter T Kan,Marco Colasurdo,Gaultier Marnat,Jérôme Berge,Xavier Barreau,Igor Sibon,Simona Nedelcu,Nils Henninger,Maéva Kyheng,Thomas R Marotta,Christopher J Stapleton,James D Rabinov,Takahiro Ota,Shogo Dofuku,Leonard Ll Yeo,Benjamin Yq Tan,Juan Carlos Martinez-Gutierrez,Sergio Salazar-Marioni,Sunil Sheth,Leonardo Renieri,Carolina Capirossi,Ashkan Mowla,Stavropoula I Tjoumakaris,Pascal Jabbour,Priyank Khandelwal,Arundhati Biswas,Frédéric Clarençon,Mahmoud Elhorany,Kevin Premat,Iacopo Valente,Alessandro Pedicelli,João Pedro Filipe,Ricardo Varela,Miguel Quintero-Consuegra,Nestor R Gonzalez,Markus A Möhlenbruch,Jessica Jesser,Illario Tancredi,Adrien Ter Schiphorst,Vivek Yedavalli,Pablo Harker,Lina M Chervak,Yasmin Aziz,Benjamin Gory,Christian Paul Stracke,Constantin Hecker,Monika Killer-Oberpfalzer,Christoph J Griessenauer,Ajith J Thomas,Cheng-Yang Hsieh,David S Liebeskind,Andrea M Alexandre,Tobias D Faizy,Charlotte Weyland,Aman B Patel,Vitor Mendes Pereira,Boris Lubicz,Adam A Dmytriw,Adrien Guenego

Source: European stroke journal

CONCLUSION: Over 2/3 of patients with MeVOs and FPE in our cohort had a favorable outcome at 90 days. FPE is independently associated with favorable outcomes, it may reduce the risk of any intracranial hemorrhage, and 3-month mortality.

Appendicular lean mass index changes in patients with Duchenne muscular dystrophy and Becker muscular dystrophy

miércoles, octubre 25, 2023

Author(s): Brenda L Wong,Suzanne Summer,Paul S Horn,Meilan M Rutter,Irina Rybalsky,Cuixia Tian,Karen C Shellenbarger,Heidi J Kalkwarf

Source: Journal of cachexia, sarcopenia and muscle

CONCLUSIONS: Age-related changes in ALMI in patients with BMD and intermediate DMD differ from those with typical DMD, reflecting their clinical phenotypes. ALM and ALMI should be further studied in patients with BMD and DMD subtypes for their potential value as surrogate markers to characterize the severity of BMD and DMD and inform clinical care decisions and clinical trial designs.

Prevalence and predictors of shared decision-making in goals-of-care clinician-family meetings for critically ill neurologic patients: a multi-center mixed-methods study

sábado, octubre 21, 2023

Author(s): Victoria Fleming,Abhinav Prasad,Connie Ge,Sybil Crawford,Shazeb Meraj,Catherine L Hough,Bernard Lo,Shannon S Carson,Jay Steingrub,Douglas B White,Susanne Muehlschlegel

Source: Critical care (London, England)

CONCLUSION: Fewer than 1 in 10 goals-of-care clinician-family meetings for critically ill neurological patients contained all shared decision-making elements. Our findings highlight gaps in shared decision-making. Interventions promoting shared decision-making for high-stakes decisions in these patients may increase patient-value congruent care; future studies should also examine whether they will affect decision quality and surrogates' health outcomes.

Loss of TDP-43 function contributes to genomic instability in amyotrophic lateral sclerosis

miércoles, octubre 18, 2023

Author(s): Minggang Fang,Sara K Deibler,Alissa L Nana,Sarat C Vatsavayai,Shahid Banday,You Zhou,Sandra Almeida,Alexandra Weiss,Robert H Brown,William W Seeley,Fen-Biao Gao,Michael R Green

Source: Frontiers in neuroscience

A common pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the cytoplasmic mislocalization and aggregation of the DNA/RNA-binding protein TDP-43, but how loss of nuclear TDP-43 function contributes to ALS and FTD pathogenesis remains largely unknown. Here, using large-scale RNAi screening, we identify TARDBP, which encodes TDP-43, as a gene whose loss-of-function results in elevated DNA mutation rate and genomic instability. Consistent with this...

Successful Mechanical Thrombectomy of Bilateral Middle Cerebral Artery Occlusions Following Apixaban Discontinuation

lunes, octubre 16, 2023

Author(s): Bahadar S Srichawla,Ton Fang,Abigail Bose,Vincent Kipkorir,Annie Ferris

Source: Journal of investigative medicine high impact case reports

Optimal anticoagulation management in patients with atrial fibrillation (AF) during acute ischemic stroke is complex and often poses a significant clinical challenge. An 82-year-old man with AF presented with left-sided hemiparesis and hypoesthesia due to occlusion of the right middle cerebral artery (MCA) after discontinuing apixaban for 5 days. Successful mechanical thrombectomy (MT) achieved thrombolysis in cerebral infarction (TICI) score of 2C. Anticoagulation was postponed due to a small...

Death after High-Dose rAAV9 Gene Therapy in a Patient with Duchenne's Muscular Dystrophy

miércoles, septiembre 27, 2023

Author(s): Angela Lek,Brenda Wong,Allison Keeler,Meghan Blackwood,Kaiyue Ma,Shushu Huang,Katelyn Sylvia,A Rita Batista,Rebecca Artinian,Danielle Kokoski,Shestruma Parajuli,Juan Putra,C Katte Carreon,Hart Lidov,Keryn Woodman,Sander Pajusalu,Janelle M Spinazzola,Thomas Gallagher,Joan LaRovere,Diane Balderson,Lauren Black,Keith Sutton,Richard Horgan,Monkol Lek,Terence Flotte

Source: The New England journal of medicine

We treated a 27-year-old patient with Duchenne's muscular dystrophy (DMD) with recombinant adeno-associated virus (rAAV) serotype 9 containing dSaCas9 (i.e., "dead" Staphylococcus aureus Cas9, in which the Cas9 nuclease activity has been inactivated) fused to VP64; this transgene was designed to up-regulate cortical dystrophin as a custom CRISPR-transactivator therapy. The dose of rAAV used was 1×10^(14) vector genomes per kilogram of body weight. Mild cardiac dysfunction and pericardial...

Delayed Diagnosis in Cerebral Venous Thrombosis: Associated Factors and Clinical Outcomes

miércoles, septiembre 27, 2023

Author(s): Ekaterina Bakradze,Liqi Shu,Nils Henninger,Shyam Prabhakaran,James E Siegler,Gian Marco De Marchis,James A Giles,Tolga Dittrich,Mirjam R Heldner,Kateryna Antonenko,Wayneho Kam,David S Liebeskind,Alexis N Simpkins,Thanh N Nguyen,Shadi Yaghi,Ava L Liberman

Source: Journal of the American Heart Association

Background Identifying factors associated with delayed diagnosis of cerebral venous thrombosis (CVT) can inform future strategies for early detection. Methods and Results We conducted a retrospective cohort study including all participants from ACTION-CVT (Anticoagulation in the Treatment of Cerebral Venous Thrombosis) study who had dates of neurologic symptom onset and CVT diagnosis available. Delayed diagnosis was defined as CVT diagnosis occurring in the fourth (final) quartile of days from...

Artificial microRNA suppresses C9ORF72 variants and decreases toxic dipeptide repeat proteins in vivo

martes, septiembre 26, 2023

Author(s): Gabriela Toro Cabrera,Katharina E Meijboom,Abbas Abdallah,Helene Tran,Zachariah Foster,Alexandra Weiss,Nicholas Wightman,Rachel Stock,Tania Gendron,Alisha Gruntman,Anthony Giampetruzzi,Leonard Petrucelli,Robert H Brown,Christian Mueller

Source: Gene therapy

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects motor neurons, causing progressive muscle weakness and respiratory failure. The presence of an expanded hexanucleotide repeat in chromosome 9 open reading frame 72 (C9ORF72) is the most frequent mutation causing familial ALS and frontotemporal dementia (FTD). To determine if suppressing expression of C9ORF72 gene products can reduce toxicity, we designed a set of artificial microRNAs (amiRNA) targeting the...

Reliable multiplex generation of pooled induced pluripotent stem cells

martes, septiembre 26, 2023

Author(s): Molly Smullen,Meagan N Olson,Julia M Reichert,Pepper Dawes,Liam F Murray,Christina E Baer,Qi Wang,Benjamin Readhead,George M Church,Elaine T Lim,Yingleong Chan

Source: Cell reports methods

Reprogramming somatic cells into pluripotent stem cells (iPSCs) enables the study of systems in vitro. To increase the throughput of reprogramming, we present induction of pluripotency from pooled cells (iPPC)-an efficient, scalable, and reliable reprogramming procedure. Using our deconvolution algorithm that employs pooled sequencing of single-nucleotide polymorphisms (SNPs), we accurately estimated individual donor proportions of the pooled iPSCs. With iPPC, we concurrently reprogrammed over...

Author Correction: Guidelines for Neuroprognostication in Adults with Guillain-Barré Syndrome

martes, septiembre 19, 2023

Author(s): Katharina M Busl,Herbert Fried,Susanne Muehlschlegel,Katja E Wartenberg,Venkatakrishna Rajajee,Sheila A Alexander,Claire J Creutzfeldt,Gabriel V Fontaine,Sara E Hocker,David Y Hwang,Keri S Kim,Dominik Madzar,Dea Mahanes,Shraddha Mainali,Juergen Meixensberger,Oliver W Sakowitz,Panayiotis N Varelas,Thomas Westermaier,Christian Weimar

Source: Neurocritical care

No abstract

Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Goals-of-Care and Family/Surrogate Decision-Maker Data

miércoles, septiembre 13, 2023

Author(s): Matthew N Jaffa,Hannah L Kirsch,Claire J Creutzfeldt,Mary Guanci,David Y Hwang,Darlene LeTavec,Dea Mahanes,Girija Natarajan,Alexis Steinberg,Darin B Zahuranec,Susanne Muehlschlegel,Curing Coma Campaign Collaborators

Source: Neurocritical care

CONCLUSIONS: Our findings provide valuable CDEs specific to goals-of-care decisions and family/surrogate decision-making for patients with DoC that can be used to standardize studies to generate high-quality and reproducible research in this area.

Small vessel disease is associated with later onset of major adverse cardiovascular events after acute cervicocerebral artery dissection

miércoles, septiembre 13, 2023

Author(s): Jayachandra Muppa,Muhammed E Gunduz,Rozaleen Aleyadeh,Shadi Yaghi,Liqi Shu,Nils Henninger

Source: Journal of the neurological sciences

CONCLUSION: Severe CSVD burden was associated with a significantly greater risk of late MACE. CSVD assessment in CAD patients may aid risk stratification and treatment optimization.

Translation of dipeptide repeat proteins in C9ORF72 ALS/FTD through unique and redundant AUG initiation codons

jueves, septiembre 07, 2023

Author(s): Yoshifumi Sonobe,Soojin Lee,Gopinath Krishnan,Yuanzheng Gu,Deborah Y Kwon,Fen-Biao Gao,Raymond P Roos,Paschalis Kratsios

Source: eLife

A hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A hallmark of ALS/FTD pathology is the presence of dipeptide repeat (DPR) proteins, produced from both sense GGGGCC (poly-GA, poly-GP, poly-GR) and antisense CCCCGG (poly-PR, poly-PG, poly-PA) transcripts. Translation of sense DPRs, such as poly-GA and poly-GR, depends on non-canonical (non-AUG) initiation codons. Here, we provide evidence for...

Mature iPSC-derived astrocytes of an ALS/FTD patient carrying the TDP43A90V mutation display a mild reactive state and release polyP toxic to motoneurons

miércoles, agosto 30, 2023

Author(s): Fabiola Rojas,Rodrigo Aguilar,Sandra Almeida,Elsa Fritz,Daniela Corvalán,Estibaliz Ampuero,Sebastián Abarzúa,Polett Garcés,Armando Amaro,Iván Diaz,Cristian Arredondo,Nicole Cortes,Mario Sanchez,Constanza Mercado,Lorena Varela-Nallar,Fen-Biao Gao,Martin Montecino,Brigitte van Zundert

Source: Frontiers in cell and developmental biology

Astrocytes play a critical role in the maintenance of a healthy central nervous system and astrocyte dysfunction has been implicated in various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). There is compelling evidence that mouse and human ALS and ALS/FTD astrocytes can reduce the number of healthy wild-type motoneurons (MNs) in co-cultures or after treatment with astrocyte conditioned media (ACM), independently of their genotype. A...

Amyotrophic lateral sclerosis

jueves, agosto 24, 2023

Author(s): David S Younger,Robert H Brown

Source: Handbook of clinical neurology

The scientific landscape surrounding amyotrophic lateral sclerosis has shifted immensely with a number of well-defined ALS disease-causing genes, each with related phenotypical and cellular motor neuron processes that have come to light. Yet in spite of decades of research and clinical investigation, there is still no etiology for sporadic amyotrophic lateral sclerosis, and treatment options even for those with well-defined familial syndromes are still limited. This chapter provides a...

Loss of function of the ALS-associated NEK1 kinase disrupts microtubule homeostasis and nuclear import

miércoles, agosto 16, 2023

Author(s): Jacob R Mann,Elizabeth D McKenna,Darilang Mawrie,Vasileios Papakis,Francesco Alessandrini,Eric N Anderson,Ryan Mayers,Hannah E Ball,Evan Kaspi,Katherine Lubinski,Desiree M Baron,Liana Tellez,John E Landers,Udai B Pandey,Evangelos Kiskinis

Source: Science advances

Loss-of-function variants in NIMA-related kinase 1 (NEK1) constitute a major genetic cause of amyotrophic lateral sclerosis (ALS), accounting for 2 to 3% of all cases. However, how NEK1 mutations cause motor neuron (MN) dysfunction is unknown. Using mass spectrometry analyses for NEK1 interactors and NEK1-dependent expression changes, we find functional enrichment for proteins involved in the microtubule cytoskeleton and nucleocytoplasmic transport. We show that α-tubulin and importin-β1, two...

An Adjustable Magnetic Levator Prosthesis for Customizable Eyelid Re-Animation in Severe Blepharoptosis: Design and Proof-of-Concept

viernes, agosto 11, 2023

Author(s): Nish Mohith Kurukuti,Melanie Nadeau,Eleftherios I Paschalis,Kevin E Houston

Source: Translational vision science & technology

CONCLUSIONS: Preliminary results suggest that the an aMLP can correct ptosis without adversely affecting blink function. Further evaluation in a larger patient population is warranted.

Repeated mild traumatic brain injury triggers pathology in asymptomatic C9ORF72 transgenic mice

martes, agosto 01, 2023

Author(s): Aydan Kahriman,James Bouley,Idil Tuncali,Elif O Dogan,Mariana Pereira,Thuyvan Luu,Daryl A Bosco,Samer Jaber,Owen M Peters,Robert H Brown,Nils Henninger

Source: Brain : a journal of neurology

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal neurodegenerative diseases that represent ends of the spectrum of a single disease. The most common genetic cause of FTD and ALS is a hexanucleotide repeat expansion in the C9orf72 gene. Although epidemiological data suggest that traumatic brain injury (TBI) represents a risk factor for FTD and ALS, its role in exacerbating disease onset and course remains unclear. To explore the interplay between traumatic brain...

Life-Limiting Peripheral Organ Dysfunction in Feline Sandhoff Disease Emerges after Effective CNS Gene Therapy

martes, agosto 01, 2023

Author(s): Aime K Johnson,Victoria J McCurdy,Heather L Gray-Edwards,Anne S Maguire,J Nicholas Cochran,Amanda L Gross,Haleigh E Skinner,Ashley N Randle,Jamie L Shirley,Brandon L Brunson,Allison M Bradbury,Stanley G Leroy,Misako Hwang,Hannah E Rockwell,Nancy R Cox,Henry J Baker,Thomas N Seyfried,Miguel Sena-Esteves,Douglas R Martin

Source: Annals of neurology

OBJECTIVE: GM2 gangliosidosis is usually fatal by 5 years of age in its 2 major subtypes, Tay-Sachs and Sandhoff disease. First reported in 1881, GM2 gangliosidosis has no effective treatment today, and children succumb to the disease after a protracted neurodegenerative course and semi-vegetative state. This study seeks to further develop adeno-associated virus (AAV) gene therapy for human translation.

Thematic Analysis of Psychosocial Stressors and Adaptive Coping Strategies Among Informal Caregivers of Patients Surviving ICU Admission for Coma

lunes, julio 31, 2023

Author(s): David Y Hwang,Sarah M Bannon,Kate Meurer,Rina Kubota,Nithyashri Baskaran,Jisoo Kim,Qiang Zhang,Mira Reichman,Nathan S Fishbein,Kaitlyn Lichstein,Melissa Motta,Susanne Muehlschlegel,Michael E Reznik,Matthew N Jaffa,Claire J Creutzfeldt,Corey R Fehnel,Amanda D Tomlinson,Craig A Williamson,Ana-Maria Vranceanu,COMA-F Investigators

Source: Neurocritical care

CONCLUSIONS: In response to substantial stressors, family caregivers of patients with SABI attempted to enact various psychological and behavioral coping strategies. They described avoidance and distraction as less helpful than other coping strategies but had difficulty engaging in alternative strategies because of their emotional distress. These findings can directly inform the development of additional resources to mitigate the long-term impact of acute psychological distress among this...

Voice Acoustic Instability During Spontaneous Speech in Parkinson's Disease

jueves, julio 27, 2023

Author(s): Kara M Smith,Meaghan Demers-Peel,Christina Manxhari,Cara E Stepp

Source: Journal of voice : official journal of the Voice Foundation

CONCLUSIONS: Mean and STSD f(o) as well as CPPS may be sensitive to PD-MCI status in reading and spontaneous speech tasks. Speech motor instability can be observed in these voice acoustic parameters over brief speech tasks, but the degree of decline does not depend on cognitive status. These findings will inform the ongoing development of algorithms to monitor speech and cognitive function in PD.

Editorial for the Neurogenetics and Neurogenomics special issue

jueves, julio 20, 2023

Author(s): Elaine T Lim,Yingleong Chan

Source: Human genetics

No abstract

Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Goals-of-care and Family/Surrogate Decision-Maker Data

martes, julio 18, 2023

Author(s): Matthew N Jaffa,Hannah L Kirsch,Claire J Creutzfeldt,Mary Guanci,David Y Hwang,Darlene LeTavec,Dea Mahanes,Alexis Steinberg,Girija Natarajan,Darin B Zahuranec,Susanne Muehlschlegel

Source: Research square

CONCLUSIONS: Our findings provide valuable CDEs specific to goals-of-care decisions and family/surrogate decision-making for patients with DoC that can be used to standardize studies to generate high-quality and reproducible research in this area.

Improving Access to Specialist Palliative Care for Patients With Catastrophic Strokes Using Best Practice Advisory- a Feasibility Study

jueves, julio 13, 2023

Author(s): Vandana Nagpal,Marcey L Osgood,Jennifer Reidy,Rose Healy,Brian Silver

Source: The Neurohospitalist

BACKGROUND AND PURPOSE: The American Heart Association and American Stroke Association (AHA/ASA) strongly recommend specialty palliative care (PC) for all patients hospitalized with life-threatening or life-altering strokes to provide expert symptom management, improve communication, promote shared decision-making and relieve suffering. We piloted an intervention to remind physicians about high PC needs of their patients admitted with catastrophic stroke.

Craniocervical junction intradural extramedullary meningioma with cord compression

miércoles, julio 12, 2023

Author(s): Bahadar S Srichawla,Hande Can,Wissam Deeb

Source: BMJ case reports

Craniocervical spine meningiomas are rare. They often present with non-specific motor or sensory symptoms. Presenting symptoms can include gait ataxia, radiculopathy, myelopathy, back pain and sensory deficits. Spinal meningiomas are slow-growing tumours, with an insidious onset. Due to the critical location of craniocervical meningiomas, severe symptoms such as respiratory distress and quadriparesis are possible. We describe the clinical presentation of a craniocervical junction meningioma, its...

Outcomes of Telestroke Inter-Hospital Transfers Among Intervention and Non-Intervention Patients

miércoles, julio 12, 2023

Author(s): Adalia H Jun-O'Connell,Shravan Sivakumar,Nils Henninger,Brian Silver,Meghna Trivedi,Mehdi Ghasemi,Rakhee R Lalla,Kimiyoshi J Kobayashi

Source: Journal of clinical medicine research

CONCLUSIONS: Telestroke is a valuable resource that expedites emergent neurological care via referral to a stroke center. However, not all transferred patients benefit from the transfer process. Future multicenter studies are warranted to study the effects or appropriateness of telestroke networks, and to better understand the patient characteristics, resources allocation, and transferring institutions to improve telestroke care.

Tetraspanin CD82 Associates with Trafficking Vesicle in Muscle Cells and Binds to Dysferlin and Myoferlin

miércoles, julio 12, 2023

Author(s): Tatiana Fontelonga,Arielle J Hall,Jaedon L Brown,Youngsook L Jung,Matthew S Alexander,Janice A Dominov,Vincent Mouly,Natassia Vieira,Mayana Zatz,Mariz Vainzof,Emanuela Gussoni

Source: Advanced biology

Tetraspanins organize protein complexes at the cell membrane and are responsible for assembling diverse binding partners in changing cellular states. Tetraspanin CD82 is a useful cell surface marker for prospective isolation of human myogenic progenitors and its expression is decreased in Duchenne muscular dystrophy (DMD) cell lines. The function of CD82 in skeletal muscle remains elusive, partly because the binding partners of this tetraspanin in muscle cells have not been identified....

Neurological diseases in intensive care

lunes, julio 10, 2023

Author(s): Virginia Newcombe,Susanne Muehlschlegel,Romain Sonneville

Source: Intensive care medicine

No abstract

ASCEND: A randomized controlled trial of titration strategies for vagus nerve stimulation in drug-resistant epilepsy

lunes, julio 10, 2023

Author(s): Anto I Bagić,Ryan Verner,Pegah Afra,Selim Benbadis,ASCEND Study Group

Source: Epilepsy & behavior : E&B

Vagus Nerve Stimulation (VNS) therapy is widely understood to provide clinically meaningful improvements in seizure control to patients with drug-resistant epilepsy, and has been a staple in the clinical armamentaria available to epileptologists for over 25 years. Despite the long history of evidence-based reviews by neurology professional societies, there is still evidence of a practice gap in VNS titration and dosing that aims to maximize clinical benefit. Recent retrospective analyses have...

Clinical validation of a multi-protein, serum-based assay for disease activity assessments in multiple sclerosis

jueves, julio 06, 2023

Author(s): Tanuja Chitnis,John Foley,Carolina Ionete,Nabil K El Ayoubi,Shrishti Saxena,Patricia Gaitan-Walsh,Hrishikesh Lokhande,Anu Paul,Fermisk Saleh,Howard Weiner,Ferhan Qureshi,Michael J Becich,Fatima Rubio da Costa,Victor M Gehman,Fujun Zhang,Anisha Keshavan,Kian Jalaleddini,Ati Ghoreyshi,Samia J Khoury

Source: Clinical immunology (Orlando, Fla.)

An 18-protein multiple sclerosis (MS) disease activity (DA) test was validated based on associations between algorithm scores and clinical/radiographic assessments (N = 614 serum samples; Train [n = 426; algorithm development] and Test [n = 188; evaluation] subsets). The multi-protein model was trained based on presence/absence of gadolinium-positive (Gd+) lesions and was also strongly associated with new/enlarging T2 lesions, and active versus stable disease (composite of radiographic and...

Stroke nurse navigator utilization reduces unplanned 30-day readmission in stroke patients treated with thrombolysis

lunes, julio 03, 2023

Author(s): Adalia H Jun-O'Connell,Eliza Grigoriciuc,Akanksha Gulati,Brian Silver,Kimiyoshi J Kobayashi,Majaz Moonis,Nils Henninger

Source: Frontiers in neurology

CONCLUSION: The utilization of a stroke nurse navigator team reduced unplanned 30-day readmissions in stroke patients treated with thrombolysis. Further studies are warranted to determine the extent of the results of stroke patients not treated with thrombolysis and to better understand the relationship between resource utilization during the transition period from discharge and quality outcomes in stroke.

Genome-wide structural variant analysis identifies risk loci for non-Alzheimer's dementias

viernes, junio 30, 2023

Author(s): Karri Kaivola,Ruth Chia,Jinhui Ding,Memoona Rasheed,Masashi Fujita,Vilas Menon,Ronald L Walton,Ryan L Collins,Kimberley Billingsley,Harrison Brand,Michael Talkowski,Xuefang Zhao,Ramita Dewan,Ali Stark,Anindita Ray,Sultana Solaiman,Pilar Alvarez Jerez,Laksh Malik,Ted M Dawson,Liana S Rosenthal,Marilyn S Albert,Olga Pletnikova,Juan C Troncoso,Mario Masellis,Julia Keith,Sandra E Black,Luigi Ferrucci,Susan M Resnick,Toshiko Tanaka,American Genome Center,International LBD Genomics Consortium,International ALS/FTD Consortium,PROSPECT Consortium,Eric Topol,Ali Torkamani,Pentti Tienari,Tatiana M Foroud,Bernardino Ghetti,John E Landers,Mina Ryten,Huw R Morris,John A Hardy,Letizia Mazzini,Sandra D'Alfonso,Cristina Moglia,Andrea Calvo,Geidy E Serrano,Thomas G Beach,Tanis Ferman,Neill R Graff-Radford,Bradley F Boeve,Zbigniew K Wszolek,Dennis W Dickson,Adriano Chiò,David A Bennett,Philip L De Jager,Owen A Ross,Clifton L Dalgard,J Raphael Gibbs,Bryan J Traynor,Sonja W Scholz

Source: Cell genomics

We characterized the role of structural variants, a largely unexplored type of genetic variation, in two non-Alzheimer's dementias, namely Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced structural variant calling pipeline (GATK-SV) to short-read whole-genome sequence data from 5,213 European-ancestry cases and 4,132 controls. We discovered, replicated, and validated a deletion in TPCN1 as a novel risk locus for...

Telemedicine impact on post-stroke outpatient follow-up in an academic healthcare network during the COVID-19 pandemic

jueves, junio 29, 2023

Author(s): Darwish Alabyad,Manet Lemuel-Clarke,Marlyn Antwan,Laura Henriquez,Samir Belagaje,Srikant Rangaraju,Ashlee Mosley,Jacqueline Cabral,Teri Walczak,Moges Ido,Patricia Hashima,Rana Bayakly,Kathyrn Collins,Loretta Sutherly-Bhadsavle,Cynthia Brasher,Elham Danaie,Patricia Victor,Deborah Westover,Mark Webb,Susana Skukalek,A M Barrett,Gregory J Esper,Fadi Nahab

Source: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association

CONCLUSIONS: Despite telemedicine implementation at an academic healthcare network successfully increasing post-stroke discharge follow-up in a centralized subspecialty stroke clinic, the majority of patients did not complete 90-day follow-up during the COVID-19 pandemic.

Early chromosome condensation by XIST builds A-repeat RNA density that facilitates gene silencing

jueves, junio 29, 2023

Author(s): Melvys Valledor,Meg Byron,Brett Dumas,Dawn M Carone,Lisa L Hall,Jeanne B Lawrence

Source: Cell reports

XIST RNA triggers chromosome-wide gene silencing and condenses an active chromosome into a Barr body. Here, we use inducible human XIST to examine early steps in the process, showing that XIST modifies cytoarchitecture before widespread gene silencing. In just 2-4 h, barely visible transcripts populate the large "sparse zone" surrounding the smaller "dense zone"; importantly, density zones exhibit different chromatin impacts. Sparse transcripts immediately trigger immunofluorescence for...

Modeling of mitochondrial genetic polymorphisms reveals induction of heteroplasmy by pleiotropic disease locus 10398A>G

martes, junio 27, 2023

Author(s): Molly Smullen,Meagan N Olson,Liam F Murray,Madhusoodhanan Suresh,Guang Yan,Pepper Dawes,Nathaniel J Barton,Jivanna N Mason,Yucheng Zhang,Aria A Fernandez-Fontaine,George M Church,Diego Mastroeni,Qi Wang,Elaine T Lim,Yingleong Chan,Benjamin Readhead

Source: Scientific reports

Mitochondrial (MT) dysfunction has been associated with several neurodegenerative diseases including Alzheimer's disease (AD). While MT-copy number differences have been implicated in AD, the effect of MT heteroplasmy on AD has not been well characterized. Here, we analyzed over 1800 whole genome sequencing data from four AD cohorts in seven different tissue types to determine the extent of MT heteroplasmy present. While MT heteroplasmy was present throughout the entire MT genome for blood...

Moderate intrinsic phenotypic alterations in C9orf72 ALS/FTD iPSC-microglia despite the presence of C9orf72 pathological features

jueves, junio 22, 2023

Author(s): Ileana Lorenzini,Eric Alsop,Jennifer Levy,Lauren M Gittings,Deepti Lall,Benjamin E Rabichow,Stephen Moore,Ryan Pevey,Lynette M Bustos,Camelia Burciu,Divya Bhatia,Mo Singer,Justin Saul,Amanda McQuade,Makis Tzioras,Thomas A Mota,Amber Logemann,Jamie Rose,Sandra Almeida,Fen-Biao Gao,Michael Marks,Christopher J Donnelly,Elizabeth Hutchins,Shu-Ting Hung,Justin Ichida,Robert Bowser,Tara Spires-Jones,Mathew Blurton-Jones,Tania F Gendron,Robert H Baloh,Kendall Van Keuren-Jensen,Rita Sattler

Source: Frontiers in cellular neuroscience

While motor and cortical neurons are affected in C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), it remains largely unknown if and how non-neuronal cells induce or exacerbate neuronal damage. We differentiated C9orf72 ALS/FTD patient-derived induced pluripotent stem cells into microglia (iPSC-MG) and examined their intrinsic phenotypes. Similar to iPSC motor neurons, C9orf72 ALS/FTD iPSC-MG mono-cultures form G(4)C(2) repeat RNA foci, exhibit reduced C9orf72 protein...

Scoping Review of Multidisciplinary Care in Tourette Syndrome

lunes, junio 19, 2023

Author(s): Samantha Willford,Wissam Deeb

Source: Movement disorders clinical practice

CONCLUSIONS: A multidisciplinary care model for TS is the preferred model advocated by patients, physicians, and organizations. This scoping review reveals that the impetus for multidisciplinary care rests on four primary benefits, but there is a lack of empirical evidence for defining and evaluating its use.

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