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The reduction of sleep-like perilesional cortical dynamics underlies clinical recovery in stroke medRxiv. Neurol. Pub Date : 2024-03-16 Simone Sarasso, Sasha D'Ambrosio, Letizia Bernardelli, Gabriel Hassan, Angela Comanducci, Piero De Giampaulis, Laura Adelaide Dalla Vecchia, Jacopo Lanzone, Marcello Massimini
Introduction. Recent studies have shown that, following brain injury, sleep-like cortical dynamics intrude into wakefulness, potentially contributing to brain network disruption and behavioral deficits. Aim. We employ TMS in combination with EEG to detect these dynamics and assess their impact on brain networks and clinical evolution in awake stroke patients. Methods. Twelve patients with subacute
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CSF proteomic profiling with amyloid/tau positivity identifies distinctive sex-different alteration of multiple proteins involved in Alzheimer disease medRxiv. Neurol. Pub Date : 2024-03-16 Anh Do, Muhammad Ali, Jigyasha Timsina, Lihua Wang, Dan Western, Menghan Liu, Jessie Sanford, Matitee Rosende-Roca, Edward N Wilson, Merce Boada, Raquel Puerta, Agustin Ruiz, Pau Pastor, Tony Wyss-Coray, Carlos Cruchaga, Yun Ju Sung
In Alzheimer s disease (AD), the most common cause of dementia, females have higher prevalence and faster progression, but sex-specific molecular findings in AD are limited. Here, we comprehensively examined and validated 7,006 aptamers targeting 6,162 proteins in cerebral spinal fluid (CSF) from 2,077 amyloid/tau positive cases and controls to identify sex-specific proteomic signatures of AD. In discovery
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Is GBA1 T369M not a risk factor for Parkinson's disease in the Swedish population? medRxiv. Neurol. Pub Date : 2024-03-16 Kajsa Atterling Brolin, David Backstrom, Joel Wallenius, Ziv Gan-Or, Andreas Puschmann, Oskar Hansson, Maria Swanberg
Variants in GBA1 are important genetic risk factors in Parkinson's disease (PD). GBA1 T369M has been linked to an ~80% increased PD risk but the reports are conflicting and the relevance of GBA1 variants in different populations varies. A lack of association between T369M and PD in the Swedish population was recently reported but needs further validation. We therefore investigated T369M in 1,808 PD
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Development of a Tremor Detection Algorithm for use in an Academic Movement Disorders Center medRxiv. Neurol. Pub Date : 2024-03-16 Mark Saad, Sofia Hefner, Suzann Donovan, Doug Bernhard, Richa Tripathi, Stewart Factor, Jeanne Powell, Hyeokhen Kwon, Reza Sameni, Christine Doss Esper, Johnathan Lucas McKay
Abstract: Tremor, defined as an "involuntary, rhythmic, oscillatory movement of a body part," is a key feature of many neurological conditions, but is still clinically assessed by visual observation. Methodologies for objectively quantifying tremor are promising but remain non-standardized across centers. Our center performs full-body behavioral testing with 3D motion capture for clinical and research
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Large-Scale Longitudinal Assessment of Declining Memory Function Through Individualized Modeling of Episodic Memory medRxiv. Neurol. Pub Date : 2024-03-16 Holly Sue Hake, Maarten van der Velde, Bridget Leonard, Thomas Grabowski, Hedderik van Rijn, Andrea Stocco
The detection and tracking of progressive memory impairments, particularly in the context of neurodegenerative disorders, relies predominantly on traditional neuropsychological assessment and short cognitive screening tools. These methods, however, are resource-intensive and lack the accessibility and/or the repeatability necessary for effective early identification and tracking interventions. This
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Genetic variation in HIF1A is associated with smoldering inflammation and disease progression in Multiple Sclerosis medRxiv. Neurol. Pub Date : 2024-03-16 Antonino Giordano, Pernilla Stridh, Paolo Preziosa, Marco Pisa, Melissa Sorosina, Elisabetta Mascia, Silvia Santoro, Kaalindi Misra, Ferdinando Clarelli, Laura Ferre', Maria Needhamsen, Ali Manouchehrinia, Miryam Cannizzaro, Thomas Moridi, Klementy Shchetynsky, Russell Ouellette, Adil Harroud, Elisabeth Sandberg, Subita Balaram Kuttikkatte, Fredrik Piehl, Lars Alfredsson, Jan Hillert, Tomas Olsson
Background: Understanding the mechanisms underlying disease progression in Multiple Sclerosis (MS) is fundamental to pave the way to treatment advances. Smoldering demyelinating inflammation characterized by iron deposition is observed at the edges of chronic active lesions and represents a relevant substrate of disease progression in MS. However, the influence of genetic factors on these mechanisms
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Increased T2 Relaxometry in Mild Traumatic Brain Injury: An Individualised Marker of Acute Neuroinflammation? medRxiv. Neurol. Pub Date : 2024-03-15 Mayan J Bedggood, Christi A Essex, Alice Theadom, Samantha J Holdsworth, Richard L.M Faull, Mangor Pedersen
Mild traumatic brain injury (mTBI), often called concussion, is a prevalent condition that can have significant implications for people's health, functioning and well-being. Current clinical practice relies on self-reported symptoms to inform return to sport, work or school decisions, which can be highly problematic. An objective technique to detect the impact of mTBI on the brain is needed. MRI-based
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Test-retest reliability of intrahemispheric dorsal premotor and primary motor cortex dual-site TMS connectivity measures medRxiv. Neurol. Pub Date : 2024-03-15 Robin Emily Heemels, Sian Ademi, Melina Hehl
Objective. Investigating the optimal interstimulus interval (ISI) and the 24-hour test-retest reliability for intrahemispheric dorsal premotor cortex (PMd) - primary motor cortex (M1) connectivity using dual-site transcranial magnetic stimulation (dsTMS). Methods. In 21 right-handed adults, left intrahemispheric PMd-M1 connectivity has been investigated with a stacked-coil dsTMS setup (conditioning
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Pure-tone audiometry and dichotic listening in primary progressive aphasia and Alzheimer's disease medRxiv. Neurol. Pub Date : 2024-03-15 Jessica Jiang, Jeremy Johnson, Benjamin A Levett, Lucy B Core, Anna Volkmer, Nehzat Koohi, Doris-Eva Bamiou, Charles R Marshall, Jason Warren, Chris Hardy
Hearing is multifaceted and the relative contributions of peripheral and central hearing loss are rarely considered together in the context of dementia. Here, we assessed peripheral (as measured with pure-tone audiometry) and central (as measured with dichotic listening) hearing in 19 patients with typical amnestic Alzheimer′s disease (tAD), 10 patients with logopenic variant primary progressive aphasia
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Dietary and Lifestyle Factors of Brain Iron Accumulation and Parkinson's Disease Risk medRxiv. Neurol. Pub Date : 2024-03-15 Jonathan Ahern, Mary ET Boyle, Wesley K. Thompson, Chun Chieh Fan, Robert Loughnan
Purpose: Iron is an essential nutrient which can only be absorbed through an individual's diet. Excess iron accumulates in organs throughout the body including the brain. Iron dysregulation in the brain is commonly associated with neurodegenerative diseases like Alzheimer's disease and Parkinson's Disease (PD). Our previous research has shown that a pattern of iron accumulation in motor regions of
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Phenotypical differentiation of tremor using time series feature extraction and machine learning medRxiv. Neurol. Pub Date : 2024-03-15 Verena Haering, Veronika Selzam, Juan Francisco Martin-Rodriguez, Petra Schwingenschuh, Gertrud Tamas, Jan Raethjen, Steffen Paschen, Franziska Goltz, Eoin Mulroy, Anna Latorre, Pablo Mir, Rick Helmich, Kailash P Bhatia, Jens Volkmann, Robert L Peach, Sebastian Schreglmann
The reliable differentiation of tremor disorders poses a significant challenge, largely depending on the subjective interpretation of subtle signs and symptoms. Given the absence of a universally accepted bio-marker, diagnostic differentiation between the most prevalent tremor disorders, Essential Tremor (ET) and tremor-dominant Parkinsons Disease (PD), frequently proves to be a non-trivial task. To
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Global Rearrangement of Degree Centrality Reflects Cognitive Impairment and Fatigue in Multiple Sclerosis medRxiv. Neurol. Pub Date : 2024-03-15 Pavel Hok, Quang Thong Thai, Barbora Rehák Bučková, Martin Domin, Kamila Řasová, Jaroslav Tintěra, Martin Lotze, Matthias Grothe, Jaroslav Hlinka
Background and Objectives: The aim of this secondary data analysis was to determine whether multiple sclerosis (MS) is associated with changes in global degree rank order disruption index (kD), a graph theory-based functional connectivity measure representing shift in overall distribution of nodal degree centrality. Additionally, we tested the relationship between kD and MS symptoms (cognitive and
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Is delirium after stroke associated with dysregulation of Hypothalamic pituitary axis? medRxiv. Neurol. Pub Date : 2024-03-15 Amanda J Barugh, Alasdair MJ MacLullich, Susan D Shenkin, Michael Allerhand, Gillian E Mead
Delirium after stroke is a serious condition associated with poorer longer term cognition. However the mechanism of delirium is poorly understood. The aberrant stress response has been postulated as a mechanism for delirium. Aim To explore the relationship between cortisol dysregulation and delirium over the first year after stroke in a prospective cohort study of patients admitted to an acute stroke
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Differential default-mode network effective connectivity in young-onset Alzheimer's disease variants medRxiv. Neurol. Pub Date : 2024-03-15 Seda Sacu, Catherine F. Slattery, Karl J. Friston, Ross W. Paterson, Alexander J.M. Foulkes, Keir Yong, Sebastian Crutch, Jonathan M. Schott, Adeel Razi
Young-onset Alzheimer's Disease(AD) is a rare form of AD characterized by early symptom onset (< 65 years) and heterogeneous clinical phenotypes. Previous studies have consistently shown that patients with late-onset AD exhibit alterations in the default mode network-a large-scale brain network associated with self-related processing and autobiographical memory. However, the functional organization
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Interoceptive disruption in functional neurological disorder: a multimodal brain imaging study medRxiv. Neurol. Pub Date : 2024-03-14 Petr Sojka, Tereza Serranova, Sahib Khalsa, David Perez, Ibai Diez
This multimodal brain imaging study investigated functional MRI (fMRI) neural processing of cardiac interoceptive signals in 38 patients with functional neurological disorder (FND) compared to 38 healthy controls (HCs). Additionally, we characterized how brain fMRI responses during heartbeat counting (interoception) vs. tone counting (exteroception) or rest related to grey matter volume, interoceptive
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Effects of Systemic Lupus Erythematosus on the Brain: A Systematic Review of Structural MRI Findings and their Relationships with Cognitive Dysfunction medRxiv. Neurol. Pub Date : 2024-03-14 Diana Valdes Cabrera, Tala El Tal, Ibrahim Mohamed, Santiago Eduardo Arciniegas, Stephanie Fevrier, Justine Ledochowski, Andrea M Knight
Background: Cognitive dysfunction (CD) is highly prevalent in systemic lupus erythematosus (SLE), yet the underlying mechanisms are poorly understood. Neuroimaging utilizing advanced magnetic resonance imaging (MRI) metrics may yield mechanistic insights. We conducted a systematic review of neuroimaging studies to investigate the relationship between structural and diffusion MRI metrics and CD in SLE
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Predictive Modeling to Uncover Parkinson's Disease Characteristics That Delay Diagnosis medRxiv. Neurol. Pub Date : 2024-03-13 Tom Haehnel, Tamara Raschka, Jochen Klucken, Enrico Glaab, Jean-Christophe Corvol, Bjoern H Falkenburger, Holger Froehlich
Background: People with Parkinson's disease (PwPD) present with a variety of motor and non-motor symptoms, and a more biological definition of PD is poised to expand the diagnostic spectrum beyond the stereotypical "elderly male with tremor". This heterogeneity can potentially pose a challenge for an accurate and early diagnosis. Objectives: To determine whether demographic or clinical characteristics
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Brain State-dependent Repetitive Transcranial Magnetic Stimulation for Motor Stroke Rehabilitation: A Proof of Concept Randomized Controlled Trial medRxiv. Neurol. Pub Date : 2024-03-12 Wala Mahmoud, David Baur, Brigitte Zrenner, Arianna Brancaccio, Paolo Belardinelli, Ander Ramos-Murguialday, Christoph Zrenner, Ulf Ziemann
Background: In healthy subjects, repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1) demonstrated plasticity effects contingent on electroencephalography (EEG)-derived excitability states, defined by the phase of the ongoing sensorimotor mu-oscillation. The therapeutic potential of brain state-dependent rTMS in the rehabilitation of upper limb motor impairment
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High fat and low carbohydrate supplies are linked to decreased epilepsy disease burden globally medRxiv. Neurol. Pub Date : 2024-03-12 Duan Ni, Alistair Senior, David Raubenheimer, Stephen Simpson, Ralph Nanan
Objectives Epilepsy is one of the major neural disorders globally. Ketogenic diets with high fat, low carbohydrate and moderate to low protein contents are well-established as interventions for epilepsy, particularly the intricate ones, exemplifying that modifying dietary compositions might have profound effects on established epilepsy. However, most of the diet-related epilepsy interventions have
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A framework for quantifying the coupling between brain connectivity and heartbeat dynamics: Insights into the disrupted network physiology in Parkinson's disease medRxiv. Neurol. Pub Date : 2024-03-11 Diego Candia-Rivera, Marie Vidailhet, Mario Chavez, Fabrizio de Vico Fallani
Parkinson's disease (PD) often shows disrupted brain connectivity and autonomic dysfunctions, progressing alongside with motor and cognitive decline. Recently, PD has been linked to a reduced sensitivity to cardiac inputs, i.e., cardiac interoception. Altogether, those signs suggest that PD causes an altered brain-heart connection whose mechanisms remain unclear. Our study aimed to explore the large-scale
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Glial activation mediates phenotypic effects of APOEe4 and sex in Alzheimer disease medRxiv. Neurol. Pub Date : 2024-03-11 Roger M Lane, Dan Li, Taher Darreh-Shori
INTRODUCTION: This study examined the impact of apolipoprotein e4 (APOEe4) allele frequency and sex on the phenotype of Alzheimer disease (AD). METHODS: The baseline characteristics, CSF, and neuroimaging biomarkers, and cognition scores collected from 45 patients aged 50-74 years with confirmed mild AD from clinical trial NCT03186989 were evaluated in a post-hoc study. RESULTS: A phenotypic spectrum
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Machine learning approach for ambient-light-corrected parameters and the Pupil Reactivity (PuRe) Score in smartphone-based pupillometry medRxiv. Neurol. Pub Date : 2024-03-11 Aleksander Bogucki, Ivo A John, Łukasz Zinkiewicz, Michał Jachura, Damian Jaworski, Karolina Suwała, Hugo Chróst, Michał Włodarski, Jakub Kałużny, Doug Campbell, Paul Bakken, Shawna Pandya, Radosław Chrapkiewicz, Sanjay G Manohar
The pupillary light reflex (PLR) is the constriction of the pupil in response to light. The PLR in response to a pulse of light follows a complex waveform that can be characterized by several parameters. It is a sensitive marker of acute neurological deterioration, but is also sensitive to the background illumination in the environment in which it is measured. To detect a pathological change in the
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Frontoparietal network integrity supports cognitive function despite atrophy and hypoperfusion in pre-symptomatic frontotemporal dementia: multimodal analysis of brain function, structure and perfusion medRxiv. Neurol. Pub Date : 2024-03-08 Xulin Liu, Simon Jones, Maurice Pasternak, Mario Masellis, Arabella Bouzigues, Lucy L. Russell, Phoebe H. Foster, Eve Ferry-Bolder, John van Swieten, Lize Jiskoot, Harro Seelaar, Raquel Sanchez-Valle, Robert Laforce, Caroline Graff, Daniela Galimberti, Rik Vandenberghe, Alexandre de Mendonca, Pietro Tiraboschi, Isabel Santana, Alexander Gerhard, Johannes Levin, Sandro Sorbi, Markus Otto, Florence Pasquier
INTRODUCTION: Gene carriers of frontotemporal dementia can remain cognitively well despite neurodegeneration. A better understanding of brain structural, perfusion and functional patterns in pre-symptomatic stage could inform accurate staging and potential mechanisms. METHODS: We included 207 pre-symptomatic carriers and 188 relatives without mutations. The grey matter volume, cerebral perfusion, and
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Recommendations for implementing the INTERACT3 care bundle for intracerebral hemorrhage in Latin America: a Delphi study medRxiv. Neurol. Pub Date : 2024-03-08 Ma.Ignacia Allende, LATAM INTERACT3 Consensus Statement Panel, Paula Muñoz-Venturelli, Francisca González, Francisca Bascur, Craig S. Anderson, Menglu Ouyang, B´ltica Cabieses, Alexandra Obach, Vanessa Cano-Nigenda, Antonio Arauz
Background and aims: The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT3) showed that the implementation of a care bundle improves outcomes after acute intracerebral hemorrhage (ICH). We aimed to establish consensus-based recommendations for the broader integration of the care bundle across Latin American countries (LAC). Methods: A 3-phase Delphi
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Accelerated brain age in young to early middle-aged adults after mild to moderate COVID-19 infection medRxiv. Neurol. Pub Date : 2024-03-07 Shelli R Kesler, Oscar Y Franco-Rocha, Alexa De La Torre Schutz, Kimberly A. Lewis, Rija Aziz, Michael Brode, Esther Melamed
Cognitive decline is a common adverse effect of the Coronavirus Disease of 2019 (COVID-19), particularly in the post-acute disease phase. The mechanisms of cognitive impairment after COVID-19 (COGVID) remain unclear, but neuroimaging studies provide evidence of brain changes, many that are associated with aging. Therefore, we calculated Brain Age Gap (BAG), which is the difference between brain age
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Self-Other Voice Discrimination Task: A - Neuropsychological Tool For Clinical Assessment of Self-Related Deficits medRxiv. Neurol. Pub Date : 2024-03-07 Philippe Voruz, Pavo Orepic, Selim Yahia Coll, Julien Haemmerli, Olaf Blanke, Julie Anne Peron, Karl Schaller, Giannina Rita Iannotti
Background. Deficits in self are commonly described through different neuro-pathologies, based on clinical evaluations and experimental paradigms. However, currently available approaches lack appropriate clinical validation, making objective evaluation and discrimination of self-related deficits challenging. Methods. We applied a statistical standardized method to assess the clinical discriminatory
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Meningeal contrast enhancement in multiple sclerosis: assessment of field strength, acquisition delay, and clinical relevance medRxiv. Neurol. Pub Date : 2024-03-07 Daniel M. Harrison, Yohance M Allette, Yuxin Zeng, Amanda Cohen, Shishir Dahal, Seongjin Choi, Jiachen Zhuo, Jun Hua
Background/Purpose Leptomeningeal enhancement (LME) on post-contrast FLAIR is described as a potential biomarker of meningeal inflammation in multiple sclerosis (MS). Here we report a comprehensive assessment of the impact of MRI field strength and acquisition timing on meningeal contrast enhancement (MCE). Methods This was a cross-sectional, observational study of 95 participants with MS and 17 healthy
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Spinal Cord Motor Neuron Phenotypes and Polygenic Risk Scores in Sporadic Amyotrophic Lateral Sclerosis: Deciphering the Disease Pathology and Therapeutic Potential of Ropinirole Hydrochloride medRxiv. Neurol. Pub Date : 2024-03-07 Chris Kato, Satoru Morimoto, Shinichi Takahashi, Shinichi Namba, Qingbo S Wang, Yukinori Okada, Hideyuki Okano
This study investigated the genetic factors associated with the onset of amyotrophic lateral sclerosis (ALS) and the mechanism of action of Ropinirole hydrochloride (ROPI) in ALS treatment. Firstly, ALS is a neurodegenerative disease characterized by the degeneration of both upper and lower motor neurons (MNs), and identifying the genetic factors of sporadic ALS (SALS) has been challenging. However
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Axonal Injury, Sleep Disturbances, and Memory following Traumatic Brain Injury medRxiv. Neurol. Pub Date : 2024-03-06 Emma M Tinney, Goretti Espana-Irla, Aaron E.L. Warren, Lauren N Whitehurst, Alexandra M Stillman, Charles H Hillman, Timothy P Morris
Objectives: Traumatic brain injury (TBI) is associated with sleep deficits, but it is not clear why some report sleep disturbances and others do not. The objective of this study was to assess the associations between axonal injury, sleep, and memory in chronic and acute TBI. Methods: To assess those with a history of TBI, 156 older adult veterans (69.8 years) from Alzheimers Disease Neuroimaging Initiative
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Comprehensive Evaluation of Artificial Intelligence Models for Diagnosis of Multiple Sclerosis Using Information from Retinal Layers Multicenter OCT Images medRxiv. Neurol. Pub Date : 2024-03-06 Zahra Khodabandeh, Hossein Rabbani, Neda Shirani Bidabadi, Mehdi Bonyani, Rahele Kafieh
Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system. Optical coherence tomography (OCT) is a retinal imaging technology with great promise as a possible MS biomarker. Unlike other ophthalmologic diseases, the variations in shape of raw cross-sectional OCTs in MS are subtle and not differentiable from healthy controls (HCs). More detailed information like
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Neurodevelopmental disorders associated variants in ADAT3 disrupt the activity of the ADAT2/ADAT3 tRNA deaminase complex and impair neuronal migration. medRxiv. Neurol. Pub Date : 2024-03-05 Jordi Del-Pozo-Rodrigez, Peggy Tilly, Romain Lecat, Hugo Rolando Vaca, Laureline Mosser, Till Balla, Marina Vitoria Gomes, Elizabeth Ramos-Morales, Elena Brivio, Thalia Salinas-Giégé, Grace VanNoy, Eleina M. England, Alysia Kern Lovgren, Melanie O'Leary, Maya Chopra, Dustin Gable, Aisha Alnuzha, Mona Kamel, Nihal Almenabawy, Anne O'Donnell-Luria, Jennifer E. Neil, Joseph G. Gleeson, Christopher A.
The ADAT2/ADAT3 complex catalyzes the adenosine to inosine modification at the wobble position of eukaryotic tRNAs. Mutations in ADAT3, the catalytically inactive subunit of the ADAT2/ADAT3 complex, have been identified in patients presenting with severe neurodevelopmental disorders (NDDs). Yet, the physiological function of ADAT2/ADAT3 complex during brain development remains totally unknown. Here
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Intracalvariosseous bone marrow injection detours the blood-brain barrier as a novel drug delivery approach for pre-clinic and clinic trials in stroke. medRxiv. Neurol. Pub Date : 2024-03-05 Wenqian Liu, Nanxing Wang, Mo Yang, Meiyang Zhang, Xiangrong Liu, Weiming Liu, Yunwei Ou, Liping Liu, Zhonghua Yang, Yanfang Liu, Mengyuan Zhou, Xiaoling Liao, Hui Qu, Fu-Dong Shi, Yuesong Pan, Chaoyu Wang, Xuezheng Feng, Xingquan Zhao, Yongjun Wang, Yilong Wang
Central nervous system (CNS) accessibility constitutes a major hurdle for drug development to treat neurological diseases. Existing drug delivery methods mainly focus on opening the blood-brain barrier (BBB) to enhance penetration. Here we show that the inherent microchannels between the skull marrow and the dura mater could be harnessed for drug delivery by intracalvariosseous (ICO) injection. Drugs
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Clinical value of plasma ALZpath pTau217 immunoassay for assessing mild cognitive impairment medRxiv. Neurol. Pub Date : 2024-03-05 Sylvain Lehmann, Susanna Schraen-Maschke, Luc Buee, Jean-Sebastien Vidal, Constance Delaby, Frederic Blanc, Claire Paquet, Bernadette Allinquant, Stephanie Bombois, Audrey Gabelle, Olivier Hanon
Objectives We sought to compare two of the most promising plasma biomarkers for Alzheimer disease (AD): pTau181 and pTau217. Methods pTau181 and pTau217 were quantified using, Quanterix and ALZpath, SIMOA assays in the well characterized prospective multicentre BALTAZAR cohort of mild cognitive impairment (MCI) participants. Results Among MCI participants, 55% were Aβ+ and 29% developed dementia due
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Meditation Experience is Associated with Increased Structural Integrity of the Pineal Gland and greater total Grey Matter maintenance medRxiv. Neurol. Pub Date : 2024-03-05 Emanuele Raffaele Giuliano Plini, Michael Christopher Melnychuk, Paul Michael Dockree
Growing evidence demonstrates that meditation practice supports cognitive functions including attention and interoceptive processing, and is associated with structural changes across cortical networks including prefrontal regions, and the insula. However, the extent of subcortical morphometric changes linked to meditation practice is less appreciated. A noteworthy candidate is the Pineal Gland, a key
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Three montages for Transcranial Electric Stimulation in predicting the early post-surgery outcome of the facial nerve functioning medRxiv. Neurol. Pub Date : 2024-03-04 Mikael Gian Andrea Izzo, Davide Rossi Sebastiano, Valentina Catanzaro, Ylenia Melillo, Ramona Togni, Elisa Visani, Jacopo Falco, Cecilia Casali, Marco Gemma, Paolo Ferroli, Annamaria Gallone, Daniele Cazzato, Grazia Devigili, Sara Alvera, Paola Lanteri
Objective: We assessed the Transcranial Electrical Stimulation (TES)-induced Corticobulbar-Motor Evoked Potentials (Cb-MEPs) evoked from Orbicularis Oculi (Oc) and Orbicularis Oris (Or) muscles with FCC5h/FCC6h-Mz, C3/C4-Cz and C5/C6/-Cz stimulation, during IntraOperative NeuroMonitoring (IONM) in 30 patients who underwent skull-base surgery. Methods: before (T0) and after (T1) the surgery, we compared
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A Systematic Review and Meta-Analysis of Automated Methods for Quantifying Enlarged Perivascular Spaces in the Brain medRxiv. Neurol. Pub Date : 2024-03-04 Jennifer M.J. Waymont, Maria Del Carmen Valdes Hernandez, Jose Bernal, Roberto Duarte Coello, Rosalind Brown, Lucia Ballerini, Francesca M. Chappell, Joanna M Wardlaw
Research into magnetic resonance imaging (MRI)- visible perivascular spaces (PVS) has recently increased, as results from studies in different diseases and populations are cementing their association with sleep, disease phenotypes, and overall health indicators. With the establishment of worldwide consortia and the availability of large databases, computational methods that allow to automatically process
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The Impact of Artificial Intelligence on Large Vessel Occlusion Stroke Detection and Management: A Systematic Review Meta-analysis medRxiv. Neurol. Pub Date : 2024-03-04 Elan Zebrowitz, Sonali Dadoo, Paige Brabant, Anaz Uddin, Esewi Aifuwa, Danielle Maraia, Mill Ettienne, Neriy Yakubov, Myoungmee Babu, Benson Babu
Introduction Stroke remains the second leading cause of death worldwide, with many survivors facing significant disabilities. In acute stroke care, the timeless adage 'Time is brain' underscores the vital need for quick action. Innovative Artificial Intelligence (AI) technology potentially offers swift detection and management of acute ischemic strokes, leading acute stroke care towards enhanced automation
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Thalamic stimulation induced changes in effective connectivity medRxiv. Neurol. Pub Date : 2024-03-04 Nicholas M Gregg, Gabriela Ojeda Valencia, Huang Harvey, Brian N Lundstrom, Jamie J Van Gompel, Kai J Miller, Gregory A Worrell, Dora Hermes
Deep brain stimulation (DBS) is a viable treatment for a variety of neurological conditions, however, the mechanisms through which DBS modulates large-scale brain networks are unresolved. Clinical effects of DBS are observed over multiple timescales. In some conditions, such as Parkinson disease and essential tremor, clinical improvement is observed within seconds. In many other conditions, such as
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Hemochromatosis Neural Archetype Reveals Iron Disruption in Motor Circuits medRxiv. Neurol. Pub Date : 2024-03-04 Robert Loughnan, Jonathan Ahern, Mary ET Boyle, Terry L Jernigan, Donald J Hagler, John R Iversen, Oleksandr Frei, Diana M Smith, Noah Zaitlen, Leo Sugrue, Wesley K Thompson, Ole Andreassen, Anders M Dale, Andrew J Schork, Chun Chieh Fan
Our understanding of brain iron regulation and its disruption in disease is currently lacking. We previously found that motor circuitry is susceptible to the cumulative neurotoxic effects of excessive iron, leading to the manifestation of Parkinson′s disease. However, beyond a few well-known genes involved in peripheral iron metabolism, the underlying molecular mechanisms regulating central iron levels
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Continuous Associations Between Remote Self-Administered Cognitive Measures and Imaging Biomarkers of Alzheimers Disease medRxiv. Neurol. Pub Date : 2024-03-02 Elizabeth A Boots, Ryan D Frank, Winnie Z Fan, Teresa J Christianson, Walter K Kremers, John L Stricker, Mary M Machulda, Julie A Fields, Jason Hassenstab, Jonathan Graff-Radford, Prashanthi Vemuri, Clifford R Jack, David S Knopman, Ronald C Petersen, Nikki H Stricker
Background: Easily accessible and self-administered cognitive assessments that can aid early detection for Alzheimers disease (AD) dementia risk are critical for timely intervention. Objectives/Design: This cross-sectional study investigated continuous associations between Mayo Test Drive (MTD) — a remote, self-administered, multi-device compatible, web-based cognitive assessment — and AD-related imaging
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Within-subjects ultra-short sleep-wake protocol for characterising circadian variations in retinal function medRxiv. Neurol. Pub Date : 2024-03-02 Hannah Sophie Heinrichs, Manuel Spitschan
Prior studies suggest that visual functions undergo time-of-day variations. Under naturalistic entrainment, diurnal changes in physiology may be driven by circadian and/or homeostatic processes, and repeated measurements at different times of day are thus not suitable to draw unambiguous conclusions about circadian effects on visual function. In this study, we disentangle circadian and homeostatic
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Pattern and mechanisms of atrophy progression in individuals with a family history of Alzheimer's disease: a comparative study medRxiv. Neurol. Pub Date : 2024-03-02 Christina Tremblay, Shady Rahayel, Alexandre Pastor-Bernier, Frederic St-Onge, Andrew Vo, Francois Rheault, Veronique Daneault, Filip Morys, Natasha Rajah, Sylvia Villeneuve, Alain Dagher, the PREVENT-AD Research Group, Alzheimer's Disease Neuroimaging Initiative ADNI
Alzheimer's disease (AD) includes a long period of presymptomatic brain changes. Different risk factors are associated with AD development, including having a family history of AD (FHAD). The Braak scheme suggests that tau pathology, in synergy with amyloid-beta (Aβ), spreads along structural connections in AD, eventually leading to atrophy. Studying the pathways in which atrophy spreads early on,
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The role of dopaminergic medication, lipid, and endocannabinoid pathway alterations in idiopathic and PRKN/PINK1-mediated Parkinson's disease - a large-scale targeted metabolomics study medRxiv. Neurol. Pub Date : 2024-03-02 Alexander Balck, Max Borsche, Philip Campbell, Xi Luo, John Harvey, Theresa Brückmann, Charlotte Ludwig, Amy Harms, Katja Lohmann, Huw Morris, Anthony H.V. Schapira, Thomas Hankemeier, Ronan Fleming, Silke Szymczak, Christine Klein
Alterations in many metabolites and biochemical pathways have been described in Parkinson's Disease (PD). However, only a small fraction of these have been replicated in independent studies. As almost every PD patient is treated with dopaminergic medication, it is challenging to discriminate between disease- and drug-related effects, especially in relation to dopamine metabolism. We conducted a large-scale
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Low-intensity repetitive transcranial magnetic stimulation is safe and well tolerated by people living with MS - outcomes of the phase I randomised controlled trial (TAURUS) medRxiv. Neurol. Pub Date : 2024-03-02 Phuong Tram Nguyen, Amin Zarghami, Kalina Makowiecki, Natasha Stevens, Chigozie Ezegbe, Kain Kyle, Chenyu Wang, Lynda Ly, Katie De La Rue, Mark Hinder, Lewis Johnson, Jennifer Rodger, Samantha Cooper, Carlie L Cullen, Michael Barnett, Kaylene Young, Bruce V Taylor
Background: Low-intensity repetitive transcranial magnetic stimulation (rTMS), delivered as a daily intermittent theta burst stimulation (iTBS) for 4 consecutive weeks, increases the number of new oligodendrocytes in the adult mouse brain. rTMS holds potential as a remyelinating intervention for people with MS. Objective: Primarily to determine the safety and tolerability of our rTMS protocol in people
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Conformal prediction enables disease course prediction and allows individualized diagnostic uncertainty in multiple sclerosis medRxiv. Neurol. Pub Date : 2024-03-02 Akshai Parakkal Sreenivasan, Aina Vaivade, Yassine Noui, Payam Emami Khoonsari, Joachim Burman, Ola Spjuth, Kim Kultima
Accurate assessment of progression and disease course in multiple sclerosis (MS) is vital for timely and appropriate clinical intervention. The transition from relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS) is gradual and diagnosed retrospectively with a typical delay of three years. To address this diagnostic delay, we developed a predictive model that is able to distinguish between
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Generalizability of trial criteria on amyloid-lowering therapy against Alzheimers disease to individuals with MCI or early AD in the general population medRxiv. Neurol. Pub Date : 2024-02-29 Jacqueline Josephine Claus, Ilse vom Hofe, Annekee van Ijlzinga Veenstra, Silvan Licher, Harro Seelaar, Frank Jan de Jong, Julia Neitzel, Meike Vernooij, Mohammad Arfan Ikram, Frank Wolters
Background Treatment with monoclonal antibodies against amyloid-beta; slowed cognitive decline in recent randomized clinical trials in patients with mild cognitive impairment (MCI) and early dementia due to Alzheimers disease (AD). However, stringent trial eligibility criteria may affect generalizability of these findings to clinical practice. Methods We extracted eligibility criteria for trials of
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Evaluation of cerebrospinal fluid alpha-synuclein seed amplification assay in PSP and CBS medRxiv. Neurol. Pub Date : 2024-02-29 David Vaughan, Riona Fumi, Marte Theilmann Jensen, Tatiana Georgiades, Lesley Wu, Danielle Lux, Ruth Obrocki, Jennifer Lamoureux, Olaf Ansorge, Kieren Allinson, Thomas T Warner, Zane Jaunmuktane, Anjum Misbahuddin, Nigel Leigh, Boyd CP Ghosh, Kailash P Bhatia, Alistair Church, Christopher Kobylecki, Michele TM Hu, James B Rowe, Cornelis Blauwendraat, Huw R Morris, Edwin Jabbari
Background: Seed amplification assay (SAA) testing has become an important biomarker in the diagnosis of alpha-synuclein related neurodegenerative disorders. Objectives: To assess the rate of alpha-synuclein SAA positivity in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), and analyse the clinical and pathological features of SAA positive and negative cases. Methods: 106 CSF samples
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Inflammatory proteins as strong predictors of death in COVID-19 patients with coexisting neurological diseases medRxiv. Neurol. Pub Date : 2024-02-29 Justyna Zielińska-Turek, Grzegorz Turek, Tomasz Lyson, Jan Gajewski, Mirosław Ząbek, Małgorzata Dorobek
Background: Although many studies published so far on COVID-19 have examined its clinical prognosis, there is still no universal laboratory test that can assess the risk of a fatal outcome in patients with coexisting neurological diseases. Methods: The plasma concentrations of C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), ferritin, interleukin 6 (IL-6), D-dimers, and highly
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Functional connectivity in preterm infants with intraventricular hemorrhage using fNIRS medRxiv. Neurol. Pub Date : 2024-02-29 Lilian M. N. Kebaya, Lingkai Tang, Talal Altamimi, Alexandra Kowalczyk, Maleb Musabi, Sriya Roychaudhuri, Homa Vahidi, Paige Meyerink, Paula Camila Mayorga, Sandrine de Ribaupierre, Soume Bhattacharya, Leandro Tristao Abi Ramia de Moraes, Keith St. Lawrence, Emma G Duerden
Introduction Intraventricular hemorrhage (IVH) is a common neurological complication following very preterm birth. Resting-state functional connectivity (RSFC) using functional magnetic resonance imaging (fMRI) is associated with injury severity; yet fMRI is impractical for use in intensive care settings. Sensitive bedside neuroimaging biomarkers are needed to characterize injury patterns. Functional
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Evaluating the effect of rapamycin treatment in Alzheimer's Disease and aging using in vivo imaging: the ERAP phase IIa clinical study protocol. medRxiv. Neurol. Pub Date : 2024-02-29 Jonas E Svensson, Martin Bolin, Daniel Thor, Pete A Williams, Rune Brautaset, Marcus Carlsson, Peder Sörensson, David Marlevi, Rubens Spin-Neto, Monika Probst, Göran Hagman, Anton Forsberg Morén, Miia Kivipelto, Pontus Plavén-Sigray
Background Rapamycin is an inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, and pre-clinical data demonstrate that it is a promising candidate for a general gero- and neuroprotective treatment in humans. Results from mouse models of Alzheimer's disease have shown beneficial effects of rapamycin including preventing or reversing cognitive deficits, reducing amyloid oligomers and
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Insights from Single-Cell RNA-seq: Identifying the Actin Gene Family as Novel Drivers in Parkinson's Disease medRxiv. Neurol. Pub Date : 2024-02-29 Saed Sayad, Mark Hiatt, Hazem Mustafa
Background. Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting millions of individuals worldwide. The complex etiology of PD involves a combination of genetic and environmental factors. The Actin family encompasses a group of highly conserved cytoskeletal proteins that play a crucial role in maintaining cellular structure and function. Actin proteins are involved
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Platform for brain network sensing and stimulation with quantitative behavioral tracking: Application to limbic circuit epilepsy medRxiv. Neurol. Pub Date : 2024-02-28 Vaclav Kremen, Vladimir Sladky, Filip Mivalt, Nicholas M Gregg, Irena M Balzekas, Tory Marks, Benjamin Henry Brinkmann, Brian Nils Lundstrom, Brian Nils Lundstrom, Richard Cui, Erik K St Louis, Paul Croarkin, Eva Alden, Julie Fields, Karla Crockett, Jindrich Adolf, Jordan Bilderbeek, Dora Hermes Miller, Steven Messina, Kai Joshua Miller, Jamie Van Gompel, Timothy Denison, Gregory A Worrell
Temporal lobe epilepsy is a common neurological disease characterized by recurrent seizures. These seizures often originate from limbic networks and people also experience chronic comorbidities related to memory, mood, and sleep (MMS). Deep brain stimulation targeting the anterior nucleus of the thalamus (ANT-DBS) is a proven therapy, but the optimal stimulation parameters remain unclear. We developed
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Association of Structural Forms of 17q21.31 with the Risk of Progressive Supranuclear Palsy and MAPT Sub-haplotypes medRxiv. Neurol. Pub Date : 2024-02-28 Hui Wang, Timothy S Chang, Beth A Dombroski, Ya-Qin Si, Catriona McLean, Alberto Tucci, Vishakha Patil, Leopoldo Valiente-Banuet, Kurt Farrell, Laura Molina-porcel, Alex Rajput, Peter Paul De Deyn, Nathalie Le Bastard, Marla Gearing, Laura Donker Kaat, John C Van Swieten, Elise Dopper, Bernardino F Ghetti, Kathy L Newell, Claire Troakes, Justo G de Yebenes, Alberto Rabano-Gutierrez, Tina Meller, Wolfgan
Importance: The chromosome 17q21.31 region, containing a 900 Kb inversion that defines H1 and H2 haplotypes, represents the strongest genetic risk locus in progressive supranuclear palsy (PSP). In addition to H1 and H2, various structural forms of 17q21.31, characterized by the copy number of α, β, and γ duplications, have been identified. However, the specific effect of each structural form on the
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A pilot study to investigate the safety and feasibility of antiretroviral therapy for Alzheimer disease (ART-AD) medRxiv. Neurol. Pub Date : 2024-02-28 Gabrielle Zuniga, Paulino Ramirez, Roman Fernandez, Chen-Pin Wang, Ji Li, Kristine Pelton, Sandra Gomez, Claira Sohn, Elias Gonzalez, Marisa Lopez-Cruzan, David A. Gonzalez, Alicia Parker, Eduardo Zilli, Gabriel A. de Erausquin, Sudha Seshadri, Sara Espinoza, Nicolas Musi, Bess Frost
Retrotransposons are viral-like DNA sequences that constitute approximately 41% of the human genome. Studies in Drosophila, mice, cultured cells, and human brain indicate that retrotransposons are activated in settings of tauopathy, including Alzheimer disease, and causally drive neurodegeneration. The antiretroviral medication 3TC (lamivudine), a nucleoside analog reverse transcriptase inhibitor,
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Metal mixtures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self-reported exposures: a case-control study medRxiv. Neurol. Pub Date : 2024-02-28 Dae Gyu Jang, John Dou, Emily J Koubek, Samuel Teener, Lili Zhou, Kelly M Bakulski, Bhramar Mukherjee, Stuart Batterman, Eva L Feldman, Stephen A Goutman
Background: The pathogenesis of amyotrophic lateral sclerosis (ALS) involves both genetic and environmental factors. This study investigates associations between metal measures in plasma and urine, ALS risk and survival, and exposure sources. Methods: Participants with and without ALS from Michigan provided plasma and urine samples for metal measurement via inductively coupled plasma mass spectrometry
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Brain volume changes following blast-related mild TBI in service members and veterans: a LIMBIC-CENC study medRxiv. Neurol. Pub Date : 2024-02-28 Emily L Dennis, Jared Rowland, Carrie Esopenko, Nicholas Tustison, Mary Newsome, Brian Avants, Jessica Gill, Sidney Hinds, Kimbra Kenney, Hannah Lindsey, Sarah Martindale-Supak, Mary Jo Pugh, Randall Scheibel, Pashtun-Poh Shahim, Robert Shih, James R Stone, Maya Troyanskaya, William C Walker, J Kent Werner, Gerald York, David Cifu, David Tate, Elisabeth A Wilde
Importance: Blast-related mild traumatic brain injuries (bTBI), the 'signature injury' of post-9/11 conflicts, are associated with clinically-relevant long-term cognitive, psychological, and behavioral dysfunction and disability; however, the underlying neural mechanisms remain unclear. Objective: To investigate associations between a history of remote bTBI and regional brain volume in a sample of
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Speech therapy combined with Cerebrolysin in enhancing aphasia recovery after acute ischemic stroke: ESCAS pilot study medRxiv. Neurol. Pub Date : 2024-02-27 Volker Hoemberg, Dragos Catalin Jianu, Adina Dora Stan, Stefan Strilciuc, Vlad-Florin Chelaru, Michał Karliński, Michael Brainin, Wolf-Dieter Heiss, Dafin F. Muresanu, Pam Enderby
Background: Stroke-induced aphasia significantly impacts communication and quality of life. Despite the standard treatment being speech and language therapy (SLT), outcomes vary, highlighting the need for additional therapies. Cerebrolysin, a neuroprotective and neurotrophic agent, has shown potential in stroke management. This study examines the effectiveness of combining Cerebrolysin with SLT in
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Endovascular thrombectomy with and without preceding thrombolysis in posterior circulation stroke – insights from STAR medRxiv. Neurol. Pub Date : 2024-02-27 Ev-Christin Heide, Sami Al Kasab, Ali M Alawieh, Adam Arthur, Waleed Brinjikji, Shakeel A Chowdhry, Roberto Crosa, Hugo H. Cuellar-Saenz, Reade A De Leacy, Travis M Dumont, Marielle Ernst, Mohamad Ezzeldin, Isabel R Fragata, Brian M Howard, Pascal M. Jabbour, Peter Kan, Joon-Tae Kim, Michael R Levitt, Justin Mascitelli, Charles Christian Matouk, Mark Moss, PEDRO NAVIA, Joshua W Osbun, Min S Park, Adam
Background: Multiple randomized trials could not establish the non-inferiority of endovascular thrombectomy (EVT) alone without preceding intravenous thrombolysis (IVT) or superiority of IVT followed by EVT in anterior circulation large vessel occlusion (LVO) stroke. The role of prior IVT in posterior circulation LVO remains controversial. Methods: In this multicenter, retrospective study, stroke patients
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Centromedian thalamic deep brain stimulation for idiopathic generalized epilepsy: case series and target analysis medRxiv. Neurol. Pub Date : 2024-02-27 Sihyeong Park, Shruti Agashe, Gamaleldin Osman, Hugh D Simpson, Kai Joshua Miller, Jamie Van Gompel, Keith Starnes, Brian Lundstrom, Greg Worrell, Nicholas M Gregg
Introduction There is a lack of treatment options for individuals with drug resistant idiopathic generalized epilepsy (IGE). Small, limited case series suggest that centromedian thalamus deep brain stimulation (CM-DBS) may be an effective treatment option. The optimal CM-DBS target for IGE is underexamined. Here, we present a retrospective analysis of CM-DBS targeting and efficacy for five patients
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Scenarios for the long-term efficacy of amyloid-targeting therapies in the context of the natural history of Alzheimer's disease medRxiv. Neurol. Pub Date : 2024-02-27 Lars Lau Raket, Jeffrey Cummings, Alexis Moscoso, Nicolas Villain, Michael Scholl
Importance: Recent clinical trials of Aβ-targeting therapies in Alzheimer's disease (AD) have demonstrated clinical benefit over 18-months, but their long-term impact on disease trajectory is not yet understood. We propose a framework for evaluating realistic long-term scenarios. Objective: To integrate data from recent phase 3 trials of the high-clearance Aβ-targeting antibodies with an estimate of