Qichao Qi, Xingang Li, Shilei Ni
No abstract text is available yet for this article.
April 1, 2021: Annals of Neurology
Alvaro Sanchez-Larsen, Alessandro Principe, Miguel Ley, Javier Navarro-Cuartero, Rodrigo Rocamora
OBJECTIVE: The link between brain function and cardiovascular dynamics is an important issue yet to be completely elucidated. The insula is a neocortical brain area that is thought to have a cardiac chronotropic regulatory function, but its role in cardiac contractility is unknown. We aim to analyze the heart rate and cardiac contractility variability after functional activation of different insular regions through direct electrical stimulation (E-stim) in humans. METHODS: Observational, prospective study, including patients admitted for stereo-electroencephalographic recording because of refractory epilepsy in whom the insular cortex was implanted...
March 30, 2021: Annals of Neurology
Hashmat Ghanizada, Mohammad Al-Mahdi Al-Karagholi, Christopher S Walker, Nanna Arngrim, Tayla Rees, Jakeb Petersen, Andrew Siow, Mette Mørch-Rasmussen, Sheryl Tan, Simon J O'Carroll, Paul Harris, Lene Theil Skovgaard, Niklas Rye Jørgensen, Margaret Brimble, Jayme S Waite, Brandon J Rea, Levi P Sowers, Andrew F Russo, Debbie L Hay, Messoud Ashina
OBJECTIVE: Migraine is a prevalent and disabling neurological disease. Its genesis is poorly understood and there remains unmet clinical need. We aimed to identify mechanisms and thus novel therapeutic targets for migraine using human models of migraine and translational models in animals, with emphasis on amylin, a close relative of calcitonin gene-related peptide (CGRP). METHODS: Thirty-six migraine without aura patients were enrolled in a randomized, double-blinded, two-way, cross-over, positive-controlled clinical trial study to receive infusion of an amylin analogue pramlintide or human αCGRP on two different experimental days...
March 27, 2021: Annals of Neurology
Ronald C Petersen, Heather J Wiste, Stephen D Weigand, Julie A Fields, Yonas E Geda, Jonathan Graff-Radford, David S Knopman, Walter K Kremers, Val Lowe, Mary Machulda, Michelle Mielke, Nikki H Stricker, Terry M Therneau, Prashanthi Vemuri, Clifford R Jack
BACKGROUND: To operationalize the National Institute on Aging-Alzheimer's Association Research Framework for Alzheimer's Disease six-stage continuum of clinical progression for persons with abnormal amyloid. METHODS: The Mayo Clinic Study of Aging is a population-based longitudinal study of aging and cognitive impairment in Olmsted County, Minnesota. We evaluated persons without dementia having three consecutive clinical visits. Measures for cross-sectional categories included objective cognitive impairment (OBJ) and function (FXN)...
March 26, 2021: Annals of Neurology
Matthew Rosebraugh, Eric A Voight, Ehab M Moussa, Feroz Jameel, Xiaochun Lou, Geoff G Z Zhang, Peter T Mayer, Deanne Stolarik, Robert A Carr, Brian P Enright, Wei Liu, Maurizio F Facheris, Philip R Kym
OBJECTIVE: To demonstrate that continuous subcutaneous infusion of a soluble levodopa (LD)/carbidopa (CD) phosphate prodrug combination effectively delivers stable LD exposure via a minimally invasive and convenient mode and has the potential to treat Parkinson's disease (PD) patients who are not well controlled on oral medication. METHODS: Foslevodopa/foscarbidopa are prepared and equilibrium solubility and chemical stability are examined in aqueous media of different pHs...
March 26, 2021: Annals of Neurology
Amanda Avona, Bianca N Mason, Carolina Burgos-Vega, Anahit H Hovhannisyan, Sergei N Belugin, Jennifer Mecklenburg, Vincent Goffin, Naureen Wajahat, Theodore J Price, Armen N Akopian, Gregory Dussor
OBJECTIVE: Migraine is three times more common in women. CGRP plays a critical role in migraine pathology and causes female-specific behavioral responses upon meningeal application. These effects are likely mediated through interactions of CGRP with signaling systems specific to females. Prolactin (PRL) levels have been correlated with migraine attacks. Here, we explore a potential interaction between CGRP and PRL in the meninges. METHODS: Prolactin, CGRP, and receptor antagonists CGRP8-37 or Δ1-9-G129R-hPRL were administered onto the dura of rodents followed by behavioral testing...
March 22, 2021: Annals of Neurology
Yun-Chu Lin, Yi-Chen Lai, Ping Chou, Shu-Wei Hsueh, Tien-Hung Lin, Chen-Syuan Huang, Ren-Wei Wang, Ya-Chin Yang, Chung-Chin Kuo
OBJECTIVE: Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy frequently associated with multiple types of seizures. The classical Na+ channel inhibitors are in general ineffective against the seizures in LGS. Rufinamide is a new Na+ channel inhibitor, but approved for the treatment of LGS. This is not consistent with a choice of antiseizure drugs (ASD) according to simplistic categorical grouping. METHODS: The effect of rufinamide on the Na+ channel, cellular discharges, and seizure behaviors were quantitatively characterized in native neurons and mammalian models of epilepsy, and compared with the other Na+ channel inhibitors...
March 21, 2021: Annals of Neurology
Sharan Paul, Warunee Dansithong, Karla P Figueroa, Mandi Gandelman, Daniel R Scoles, Stefan M Pulst
OBJECTIVE: Mutations in the ATXN2 gene (CAG expansions ≥32 repeats) can be a rare cause of Parkinson's disease and amyotrophic lateral sclerosis (ALS). We recently reported that the stress granule (SG) protein Staufen1 (STAU1) was overabundant in neurodegenerative disorder spinocerebellar ataxia type 2 (SCA2) patient cells, animal models, and ALS-TDP-43 fibroblasts, and provided a link between SG formation and autophagy. We aimed to test if STAU1 overabundance has a role in the pathogenesis of other neurodegenerative diseases...
March 21, 2021: Annals of Neurology
Orhan Aktas, Michael A Smith, William A Rees, Jeffrey L Bennett, Dewei She, Eliezer Katz, Bruce A C Cree
OBJECTIVE: Blood tests to monitor disease activity, attack severity, or treatment impact in neuromyelitis optica spectrum disorder (NMOSD) have not been developed. This study investigated the relationship between serum glial fibrillary acidic protein (sGFAP) concentration and NMOSD activity and assessed the impact of inebilizumab treatment. METHODS: N-MOmentum was a prospective, multicenter, double-blind, placebo-controlled, randomized clinical trial, in adults with NMOSD...
March 16, 2021: Annals of Neurology
Eleonora Tamilia, Margherita A G Matarrese, Georgios Ntolkeras, P Ellen Grant, Joseph R Madsen, Steve M Stufflebeam, Phillip L Pearl, Christos Papadelis
OBJECTIVE: Intracranial EEG (icEEG) studies show that interictal ripples propagate across the brain of children with medically refractory epilepsy (MRE) and the onset of this propagation (ripple-onset-zone, ROZ) estimates the epileptogenic zone. It is still unknown whether we can map this propagation non-invasively. The goal of this study is to map ripples (ripple-zone, RZ) and their propagation onset (ROZ) using high-density EEG (HD-EEG) and magnetoencephalography (MEG), and to estimate their prognostic value in pediatric epilepsy surgery...
March 12, 2021: Annals of Neurology
Adeline L Goss, Rohini D Samudralwar, Rohit R Das, Avindra Nath
No abstract text is available yet for this article.
March 12, 2021: Annals of Neurology
Lu Lin, Abrar Al-Faraj, Neishay Ayub, Pablo Bravo, Sudeshna Das, Lorenzo Ferlini, Ioannis Karakis, Jong Woo Lee, Shibani S Mukerji, Christopher R Newey, Jay Pathmanathan, Myriam Abdennadher, Charles Cassasa, Nicolas Gaspard, Daniel M Goldenholz, Emily J Gilmore, Jing Jin, Jennifer A Kim, Eyal Y Kimchi, Harshad S Ladha, Steven Tobochnik, Sahar Zafar, Lawrence J Hirsch, M Brandon Westover, Mouhsin M Shafi
OBJECTIVE: To determine the prevalence and risk factors for electrographic seizures and other EEG patterns in patients with COVID-19 undergoing clinically indicated continuous electroencephalogram monitoring (cEEG), and to assess whether EEG findings are associated with outcomes. METHODS: We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns...
March 11, 2021: Annals of Neurology
Olivia V Poole, Chiara Pizzamiglio, David Murphy, Micol Falabella, William L Macken, Enrico Bugiardini, Cathy E Woodward, Robyn Labrum, Stephanie Efthymiou, Vincenzo Salpietro, Viorica Chelban, Rauan Kaiyrzhanov, Reza Maroofian, Anthony A Amato, Allison Gregory, Susan J Hayflick, Queen Square Genomics, Hallgeir Jonvik, Nicholas Wood, Henry Houlden, Jana Vandrovcova, Michael G Hanna, Alan Pittman, Robert D S Pitceathly
A rapidly expanding catalogue of neurogenetic disorders has encouraged a diagnostic shift towards early clinical whole exome sequencing (WES). Adult primary mitochondrial diseases (PMDs) frequently exhibit neurological manifestations that overlap with other nervous system disorders. However, mitochondrial DNA (mtDNA) is not routinely analyzed in standard clinical WES bioinformatic pipelines. We reanalyzed 11,424 exomes, enriched with neurological diseases, for pathogenic mtDNA variants. Twenty-four different mtDNA mutations were detected in 64 exomes, 11 of which were considered disease causing based on the associated clinical phenotypes...
March 11, 2021: Annals of Neurology
David D Ward, Lindsay M K Wallace, Kenneth Rockwood
Risk factors for developing dementia from mild cognitive impairment (MCI) probably differ between MCI subtypes. We investigated how frailty relates to dementia risk in amnestic MCI (a-MCI; n = 2,799) and non-amnestic MCI (na-MCI; n = 629) in the National Alzheimer's Coordinating Center database. Although higher frailty increased dementia risk for people with either a-MCI or na-MCI, the larger risk was in na-MCI (interaction hazard ratio = 1.35 [95% confidence interval = 1.15-1.59], p < 0.001). Even after the onset of clinically significant cognitive impairment, poor general health, quantified by a high degree of frailty, is a significant risk for dementia...
March 11, 2021: Annals of Neurology
Bardia Nourbakhsh, Christian Cordano, Carlo Asteggiano, Klemens Ruprecht, Carolin Otto, Alice Rutatangwa, Allysa Lui, Janace Hart, Eoin P Flanagan, Judith A James, Emmanuelle Waubant
Although Epstein-Barr virus (EBV) is hypothesized to be a prerequisite for multiple sclerosis (MS), up to 15% of children with a diagnosis of MS were reported to be EBV-seronegative. When re-evaluating 25 EBV-seronegative children out of 189 pediatric patients with a diagnosis of clinically isolated syndrome/MS, we found anti-myelin oligodendrocyte glycoprotein (MOG) antibody in 11/25 (44%) EBV-seronegative, but only 9/164 (5.5%, p < 0.001) EBV-seropositive patients. After critical review, MS remained a plausible diagnosis in only four of 14 EBV-seronegative/MOG antibody-negative patients...
March 11, 2021: Annals of Neurology
Eun S Park, Sehee Kim, Shuning Huang, Ji Young Yoo, Jakob Körbelin, Tae Jin Lee, Balveen Kaur, Pramod K Dash, Peng Roc Chen, Eunhee Kim
OBJECTIVE: Brain arteriovenous malformations (bAVMs) are a leading cause of hemorrhagic stroke and neurological deficits in children and young adults, however no pharmacological intervention is available to treat these patients. Although more than 95% of bAVMs are sporadic without family history, the pathogenesis of sporadic bAVMs is largely unknown, which may account for the lack of therapeutic options. KRAS mutations are frequently observed in cancer, and a recent unprecedented finding of these mutations in sporadic human bAVMs offers a new direction in the research...
March 5, 2021: Annals of Neurology
Ann H Tilton, Jessica S Sanders
No abstract text is available yet for this article.
March 1, 2021: Annals of Neurology
Nicolas Lambert, Maximilien Steinmetz, Anne Sibille, Bernard Sadzot
No abstract text is available yet for this article.
February 27, 2021: Annals of Neurology
Ian C Wenker, Frida A Teran, Eric R Wengert, Pravin K Wagley, Payal S Panchal, Elizabeth A Blizzard, Priyanka Saraf, Jacy L Wagnon, Howard P Goodkin, Miriam H Meisler, George B Richerson, Manoj K Patel
OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is an unpredictable and devastating comorbidity of epilepsy that is believed to be due to cardiorespiratory failure immediately after generalized convulsive seizures. METHODS: We performed cardiorespiratory monitoring of seizure-induced death in mice carrying either an p.Arg1872Trp or p.Asn1768Asp mutation in a single Scn8a allele - mutations identified from patients that died from SUDEP - and by seizure-induced death of pentylenetetrazole-treated wild type mice...
February 18, 2021: Annals of Neurology
Dean M Wingerchuk, Kazuo Fujihara, Jacqueline Palace, Achim Berthele, Michael Levy, Ho Jin Kim, Ichiro Nakashima, Celia Oreja-Guevara, Kai-Chen Wang, Larisa Miller, Shulian Shang, Guido Sabatella, Marcus Yountz, Sean J Pittock
OBJECTIVE: During PREVENT (NCT01892345), eculizumab significantly reduced relapse risk versus placebo in patients with aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). We report an interim analysis of PREVENT's ongoing open-label extension (OLE; NCT02003144) evaluating eculizumab's long-term safety and efficacy. METHODS: Patients who completed PREVENT could enroll in the OLE to receive eculizumab (maintenance dose, 1200 mg/2 weeks, after a blinded induction phase)...
February 14, 2021: Annals of Neurology
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