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Single-value brain activity scores reflect both severity and risk across the Alzheimer’s continuum Brain (IF 14.5) Pub Date : 2024-05-14 Joram Soch, Anni Richter, Jasmin M Kizilirmak, Hartmut Schütze, Gabriel Ziegler, Slawek Altenstein, Frederic Brosseron, Peter Dechent, Klaus Fliessbach, Silka Dawn Freiesleben, Wenzel Glanz, Daria Gref, Michael T Heneka, Stefan Hetzer, Enise I Incesoy, Ingo Kilimann, Okka Kimmich, Luca Kleineidam, Elizabeth Kuhn, Christoph Laske, Andrea Lohse, Falk Lüsebrink, Matthias H Munk, Oliver Peters, Lukas Preis
Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional magnetic resonance imaging (fMRI) activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive aging. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer’s
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Blood–CSF barrier integrity in amyotrophic lateral sclerosis Brain (IF 14.5) Pub Date : 2024-05-14 Veronika Klose, Sarah Jesse, Jan Lewerenz, Jan Kassubek, Johannes Dorst, Angela Rosenbohm, Gabriele Nagel, Deborah Wernecke, Francesco Roselli, Hayrettin Tumani, Albert C Ludolph
The integrity of the blood-CSF barrier plays a major role in inflammation, but also in shielding the central nervous system from external and systemic – potentially toxic – factors. Here we report results of measurements of the albumin quotient – which is thought to mirror the integrity of the blood/CSF barrier - in 1059 amyotrophic lateral sclerosis patients. The results were compared with groups
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High frequency oscillations in human memory and cognition: a neurophysiological substrate of engrams? Brain (IF 14.5) Pub Date : 2024-05-14 Michal T Kucewicz, Jan Cimbalnik, Jesus S S Garcia, Milan Brazdil, Gregory A Worrell
Despite advances in understanding the cellular and molecular processes underlying memory and cognition, and recent successful modulation of cognitive performance in brain disorders, the neurophysiological mechanisms remain underexplored. High frequency oscillations beyond the classic electroencephalogram spectrum have emerged as a potential neural correlate of fundamental cognitive processes. High
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PMP22 duplication dysregulates lipid homeostasis and plasma membrane organization in developing human Schwann cells Brain (IF 14.5) Pub Date : 2024-05-14 Robert Prior, Alessio Silva, Tim Vangansewinkel, Jakub Idkowiak, Arun Kumar Tharkeshwar, Tom P Hellings, Iliana Michailidou, Jeroen Vreijling, Maarten Loos, Bastijn Koopmans, Nina Vlek, Cedrick Agaser, Thomas B Kuipers, Christine Michiels, Elisabeth Rossaert, Stijn Verschoren, Wendy Vermeire, Vincent de Laat, Jonas Dehairs, Kristel Eggermont, Diede van den Biggelaar, Adekunle T Bademosi, Frederic A
Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy caused by a 1.5 megabase tandem duplication of chromosome 17 harboring the PMP22 gene. This dose-dependent overexpression of PMP22 results in disrupted Schwann cell myelination of peripheral nerves. To get better insights into the underlying pathogenic mechanisms in CMT1A, we investigated the role of PMP22
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A mutation in the PRKAR1B gene drives pathological mechanisms of neurodegeneration across species Brain (IF 14.5) Pub Date : 2024-05-14 Tal Benjamin-Zukerman, Gilat Shimon, Marie E Gaine, Anwar Dakwar, Netta Peled, Mohammad Aboraya, Ashar Masri-Ismail, Rania Safadi-Safa, Meir Solomon, Varda Lev-Ram, Robert A Rissman, Johanna E Mayrhofer, Andrea Raffeiner, Merel O Mol, Benney M R Argue, Shaylah McCool, Binh Doan, John van Swieten, Eduard Stefan, Ted Abel, Ronit Ilouz
Protein Kinase A (PKA) neuronal function is controlled by the interaction of a regulatory (R) subunit dimer to two catalytic (C) subunits. Recently, the L50R variant in the gene encoding the RIβ subunit was identified in individuals with a novel neurodegenerative disease. However, the mechanisms driving the disease phenotype remained unknown. In this study, we generated a mouse model carrying the RIβ-L50R
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Mitigation of TDP-43 toxic phenotype by an RGNEF fragment in amyotrophic lateral sclerosis models Brain (IF 14.5) Pub Date : 2024-05-13 Cristian A Droppelmann, Danae Campos-Melo, Veronica Noches, Crystal McLellan, Robert Szabla, Taylor A Lyons, Hind Amzil, Benjamin Withers, Brianna Kaplanis, Kirti S Sonkar, Anne Simon, Emanuele Buratti, Murray Junop, Jamie M Kramer, Michael J Strong
Aggregation of the RNA-binding protein TAR DNA binding protein (TDP-43) is a hallmark of TDP-proteinopathies including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As TDP-43 aggregation and dysregulation are causative of neuronal death, there is a special interest in targeting this protein as a therapeutic approach. Previously, we found that TDP-43 extensively co-aggregated
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Neuropathy target esterase activity defines phenotypes among PNPLA6 disorders Brain (IF 14.5) Pub Date : 2024-05-13 James Liu, Yi He, Cara Lwin, Marina Han, Bin Guan, Amelia Naik, Chelsea Bender, Nia Moore, Laryssa A Huryn, Yuri V Sergeev, Haohua Qian, Yong Zeng, Lijin Dong, Pinghu Liu, Jingqi Lei, Carl J Haugen, Lev Prasov, Ruifang Shi, Hélène Dollfus, Petros Aristodemou, Yannik Laich, Andrea H Németh, John Taylor, Susan Downes, Maciej R Krawczynski, Isabelle Meunier, Melissa Strassberg, Jessica Tenney, Josephine
Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair anomalies. PNPLA6 encodes neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a systematic evidence-based review of a novel cohort
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Low-intensity ultrasound ameliorates brain organoid integration and rescues microcephaly deficits Brain (IF 14.5) Pub Date : 2024-05-13 Xiao-Hong Li, Di Guo, Li-Qun Chen, Zhe-Han Chang, Jian-Xin Shi, Nan Hu, Chong Chen, Xiao-Wang Zhang, Shuang-Qing Bao, Meng-Meng Chen, Dong Ming
Human brain organoids represent a remarkable platform for modeling neurological disorders and a promising brain repair approach. However, the effects of physical stimulation on their development and integration remain unclear. Here, we report that low-intensity ultrasound significantly increases neural progenitor cell proliferation and neuronal maturation in cortical organoids. Histological assays
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Targeting excitatory:inhibitory network imbalance in Alzheimer’s disease Brain (IF 14.5) Pub Date : 2024-05-10 David Blum, Sabine Levi
This scientific commentary refers to ‘Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer’s disease and 5XFAD mice’ by Barbour et al. (https://doi.org/10.1093/brain/awae126).
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Transient brain structure changes after high phenylalanine exposure in adults with phenylketonuria Brain (IF 14.5) Pub Date : 2024-05-09 Raphaela Muri, Christian Rummel, Richard McKinley, Michael Rebsamen, Stephanie Maissen-Abgottspon, Roland Kreis, Piotr Radojewski, Katarzyna Pospieszny, Michel Hochuli, Roland Wiest, Roman Trepp, Regula Everts
Phenylketonuria is a rare metabolic disease resulting from a deficiency of the enzyme phenylalanine hydroxylase. Recent cross-sectional evidence suggests that early-treated adults with phenylketonuria exhibit alterations in cortical grey matter compared to healthy peers. However, the effects of high phenylalanine exposure on brain structure in adulthood need to be further elucidated. In this double-blind
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Meso-cortical pathway damage in cognition, apathy and gait in cerebral small vessel disease Brain (IF 14.5) Pub Date : 2024-05-06 Hao Li, Mina A Jacob, Mengfei Cai, Roy P C Kessels, David G Norris, Marco Duering, Frank-Erik de Leeuw, Anil M Tuladhar
Cerebral small vessel disease (SVD) is known to contribute to cognitive impairment, apathy, and gait dysfunction. Although associations between cognitive impairment and either apathy or gait dysfunction have been shown in SVD, the inter-relations among these three clinical features and their potential common neural basis remains unexplored. The dopaminergic meso-cortical and meso-limbic pathways have
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Hippocampal aggregation signatures of pathogenic UBQLN2 in amyotrophic lateral sclerosis and frontotemporal dementia Brain (IF 14.5) Pub Date : 2024-05-04 Kyrah M Thumbadoo, Birger V Dieriks, Helen C Murray, Molly E V Swanson, Ji Hun Yoo, Nasim F Mehrabi, Clinton Turner, Michael Dragunow, Richard L M Faull, Maurice A Curtis, Teepu Siddique, Christopher E Shaw, Kathy L Newell, Lyndal Henden, Kelly L Williams, Garth A Nicholson, Emma L Scotter
Pathogenic variants in the UBQLN2 gene cause X-linked dominant amyotrophic lateral sclerosis and/or frontotemporal dementia characterised by ubiquilin 2 aggregates in neurons of the motor cortex, hippocampus, and spinal cord. However, ubiquilin 2 neuropathology is also seen in sporadic and familial amyotrophic lateral sclerosis and/or frontotemporal dementia cases not caused by UBQLN2 pathogenic variants
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Psilocybin reduces alcohol self-administration via selective left nucleus accumbens activation in rats Brain (IF 14.5) Pub Date : 2024-05-04 Jérôme Jeanblanc, Romain Bordy, Grégory Fouquet, Virginie Jeanblanc, Mickaël Naassila
The use of psilocybin to treat alcohol use disorder is very promising, but the mechanisms of action remain poorly understood. We combined behavioral, pharmacological and gene expression analyses to decipher the mechanisms of action of psilocybin, for the first time injected into the brain. Male Long Evans rats underwent chronic operant ethanol self-administration before testing the effect of intraperitoneal
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The brain's arbitration system and obsessional compulsive disorder Brain (IF 14.5) Pub Date : 2024-05-04 Trevor W Robbins
This scientific commentary relates to ‘Neurocomputational model of compulsivity: deviating from an uncertain goal-directed system’ by Kim et al. (https://doi.org/10.1093/brain/awae102).
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Distinct virtual histology of grey matter atrophy in four neuroinflammatory diseases Brain (IF 14.5) Pub Date : 2024-05-03 Jun Sun, Min Guo, Li Chai, Siyao Xu, Yuerong Lizhu, Yuna Li, Yunyun Duan, Xiaolu Xu, Shan Lv, Jinyuan Weng, Kuncheng Li, Fuqing Zhou, Haiqing Li, Yongmei Li, Xuemei Han, Fu-Dong Shi, Xinghu Zhang, Decai Tian, Zhizheng Zhuo, Yaou Liu
Gray matter (GM) atrophies were observed in multiple sclerosis, neuromyelitis optica spectrum disorders (both anti-aquaporin-4 antibody-positive [AQP4+], and -negative [AQP4-] subtypes NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Revealing the pathogenesis of brain atrophy in these disorders would help their differential diagnosis and guide therapeutic strategies
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Connectome reorganization associated with temporal lobe pathology and its surgical resection Brain (IF 14.5) Pub Date : 2024-05-03 Sara Larivière, Bo-yong Park, Jessica Royer, Jordan DeKraker, Alexander Ngo, Ella Sahlas, Judy Chen, Raúl Rodríguez-Cruces, Yifei Weng, Birgit Frauscher, Ruoting Liu, Zhengge Wang, Golia Shafiei, Bratislav Mišić, Andrea Bernasconi, Neda Bernasconi, Michael D Fox, Zhiqiang Zhang, Boris C Bernhardt
Network neuroscience offers a unique framework to understand the organizational principles of the human brain. Despite recent progress, our understanding of how the brain is modulated by focal lesions remains incomplete. Resection of the temporal lobe is the most effective treatment to control seizures in pharmaco-resistant temporal lobe epilepsy (TLE), making this syndrome a powerful model to study
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Hippocampal excitation-inhibition balance underlies the 5-HT2C receptor in modulating depressive behaviours Brain (IF 14.5) Pub Date : 2024-05-02 Hu-Jiang Shi, Yi-Ren Xue, Hua Shao, Cheng Wei, Ting Liu, Jie He, Yu-Hao Yang, Hong-Mei Wang, Na Li, Si-Qiang Ren, Lei Chang, Zhen Wang, Li-Juan Zhu
The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in depression is a topic of debate, and the underlying mechanisms remain largely unclear. We now elucidate hippocampal excitation-inhibition (E/I) balance underlies the regulatory effects of 5-HT2CR in depression. Molecular biological analyses showed that chronic mild stress (CMS) reduced the expression of 5-HT2CR in hippocampus. We revealed
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Congenital myasthenic syndromes in adults: clinical features, diagnosis and long-term prognosis Brain (IF 14.5) Pub Date : 2024-05-02 Julian Theuriet, Marion Masingue, Anthony Behin, Ana Ferreiro, Guillaume Bassez, Pauline Jaubert, Oriana Tarabay, Frédéric Fer, Antoine Pegat, Françoise Bouhour, Juliette Svahn, Philippe Petiot, Laurentiu Jomir, Guy Chauplannaz, Catherine Cornut-Chauvinc, Véronique Manel, Emmanuelle Salort-Campana, Shahram Attarian, Etienne Fortanier, Annie Verschueren, Ludivine Kouton, Jean-Philippe Camdessanché,
Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous diseases caused by mutations affecting neuromuscular transmission. Even if the first symptoms mainly occur during childhood, adult neurologists must confront this challenging diagnosis and manage these patients throughout their adulthood. However, long-term follow-up data from large cohorts of CMS patients are lacking
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Distinct ultrastructural phenotypes of glial and neuronal alpha-synuclein inclusions in multiple system atrophy Brain (IF 14.5) Pub Date : 2024-05-02 Carolin Böing, Marta Di Fabrizio, Domenic Burger, John G J M Bol, Evelien Huisman, Annemieke J M Rozemuller, Wilma D J van de Berg, Henning Stahlberg, Amanda J Lewis
Multiple System Atrophy is characterized pathologically by the accumulation of alpha-synuclein (aSyn) into glial cytoplasmic inclusions (GCIs). The mechanism underlying the formation of GCIs is not well understood. In this study, correlative light and electron microscopy was employed to investigate aSyn pathology in the substantia nigra and putamen of post-mortem multiple system atrophy brain donors
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How side effects can improve treatment efficacy: a randomized trial Brain (IF 14.5) Pub Date : 2024-05-01 Lieven A Schenk, Tahmine Fadai, Christian Büchel
While treatment side effects may adversely impact patients, they could also potentially function as indicators for effective treatment. In this study, we investigated whether and how side effects can trigger positive treatment expectations and enhance treatment outcomes. In this preregistered trial (DRKS00026648), 77 healthy participants were made to believe that they will receive fentanyl nasal sprays
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Characterizing brain tau and cognitive decline along the amyloid timeline in Alzheimer’s disease Brain (IF 14.5) Pub Date : 2024-04-26 Karly A Cody, Rebecca E Langhough, Matthew D Zammit, Lindsay Clark, Nathaniel Chin, Bradley T Christian, Tobey J Betthauser, Sterling C Johnson
Recent longitudinal PET imaging studies have established methods to estimate the age at which amyloid becomes abnormal at the level of the individual. Here we recontextualized amyloid levels into the temporal domain to better understand the downstream Alzheimer’s disease processes of tau neurofibrillary tangle (NFT) accumulation and cognitive decline. This cohort study included a total of 601 individuals
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Unleashing the potential of mRNA therapeutics for inherited neurological diseases Brain (IF 14.5) Pub Date : 2024-04-25 Edoardo Monfrini, Giacomo Baso, Dario Ronchi, Megi Meneri, Delia Gagliardi, Lorenzo Quetti, Federico Verde, Nicola Ticozzi, Antonia Ratti, Alessio Di Fonzo, Giacomo P Comi, Linda Ottoboni, Stefania Corti
Neurological monogenic loss-of-function diseases are hereditary disorders resulting from gene mutations that decrease or abolish the normal function of the encoded protein. These conditions pose significant therapeutic challenges, which may be resolved through the development of innovative therapeutic strategies. RNA-based technologies, such as mRNA replacement therapy, have emerged as promising and
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Revisiting distinct nerve excitability patterns in patients with amyotrophic lateral sclerosis Brain (IF 14.5) Pub Date : 2024-04-25 Diederik J L Stikvoort García, H Stephan Goedee, Ruben P A van Eijk, Leonard J van Schelven, Leonard H van den Berg, Boudewijn T H M Sleutjes
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease, characterized by loss of central and peripheral motor neurones. Although the disease is clinically and genetically heterogeneous, axonal hyperexcitability is a commonly observed feature that has been suggested to reflect an early pathophysiological step linked to the neurodegenerative cascade. Therefore, it is important to clarify
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Peripherally-derived LGI1-reactive monoclonal antibodies cause epileptic seizures in vivo Brain (IF 14.5) Pub Date : 2024-04-25 Manoj Upadhya, Toni Kirmann, Max A Wilson, Christian M Simon, Divya Dhangar, Christian Geis, Robyn Williams, Gavin Woodhall, Stefan Hallermann, Sarosh R Irani, Sukhvir K Wright
One striking clinical hallmark in patients with autoantibodies to leucine-rich glioma inactivated 1 (LGI1) is the very frequent focal seizure semiologies, including faciobrachial dystonic seizures (FBDS), in addition to the amnesia. Polyclonal serum IgGs have successfully modelled the cognitive changes in vivo but not seizures. Hence, it remains unclear whether LGI1-autoantibodies are sufficient to
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A new type of blood–brain barrier aminoacidopathy underlies metabolic microcephaly associated with SLC1A4 mutations Brain (IF 14.5) Pub Date : 2024-04-25 Maali Odeh, Clara Sajrawi, Adam Majcher, Salman Zubedat, Lihi Shaulov, Alex Radzishevsky, Liron Mizrahi, Wendy K Chung, Avi Avital, Thorsten Hornemann, Daniel J Liebl, Inna Radzishevsky, Herman Wolosker
Mutations in the SLC1A4 transporter lead to neurodevelopmental impairments, spastic tetraplegia, thin corpus callosum, and microcephaly in children. SLC1A4 catalyzes obligatory amino acid exchange between neutral amino acids, but the physiopathology of SLC1A4 disease mutations and progressive microcephaly remain unclear. Here, we examined the phenotype and metabolic profile of three Slc1a4 mouse models
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Morbidity and mortality risks associated with valproate withdrawal in young men and women with epilepsy Brain (IF 14.5) Pub Date : 2024-04-24 Gashirai K Mbizvo, Tommaso Bucci, Gregory Y H Lip, Anthony G Marson
Valproate is the most effective treatment for idiopathic generalised epilepsy. Current guidance precludes its use in women of childbearing potential, unless other treatments are ineffective or not tolerated, because of high teratogenicity. This risk was recently extended to men. New guidance will limit use both in men and women aged <55 years, resulting in withdrawal of valproate from men already taking
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A generalizable data-driven model of atrophy heterogeneity and progression in memory clinic settings Brain (IF 14.5) Pub Date : 2024-04-24 Hannah Baumeister, Jacob W Vogel, Philip S Insel, Luca Kleineidam, Steffen Wolfsgruber, Melina Stark, Helena M Gellersen, Renat Yakupov, Matthias C Schmid, Falk Lüsebrink, Frederic Brosseron, Gabriel Ziegler, Silka D Freiesleben, Lukas Preis, Luisa-Sophie Schneider, Eike J Spruth, Slawek Altenstein, Andrea Lohse, Klaus Fliessbach, Ina R Vogt, Claudia Bartels, Björn H Schott, Ayda Rostamzadeh, Wenzel
Memory clinic patients are a heterogeneous population representing various aetiologies of pathological aging. It is unknown if divergent spatiotemporal progression patterns of brain atrophy, as previously described in Alzheimer’s disease (AD) patients, are prevalent and clinically meaningful in this group of older adults. To uncover distinct atrophy subtypes, we applied the Subtype and Stage Inference
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Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer’s disease and 5XFAD mice Brain (IF 14.5) Pub Date : 2024-04-23 Aaron J Barbour, Sarah Gourmaud, Eunjoo Lancaster, Xiaofan Li, David A Stewart, Keegan F Hoag, David J Irwin, Delia M Talos, Frances E Jensen
Approximately 22% of Alzheimer’s disease (AD) patients suffer from seizures, and the co-occurrence of seizures and epileptiform activity exacerbates AD pathology and related cognitive deficits, suggesting that seizures may be a targetable component of AD progression. Given that alterations in neuronal excitatory:inhibitory (E:I) balance occur in epilepsy, we hypothesized that decreased markers of inhibition
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Expanded clinical phenotype spectrum correlates with variant function in SCN2A-related disorders Brain (IF 14.5) Pub Date : 2024-04-23 Anne T Berg, Christopher H Thompson, Leah Schust Myers, Erica Anderson, Lindsey Evans, Ariela J E Kaiser, Katherine Paltell, Amanda N Nili, Jean-Marc DeKeyser, Tatiana V Abramova, Gerry Nesbitt, Shawn Egan, Carlos G Vanoye, Alfred L George
SCN2A-related disorders secondary to altered function in the voltage-gated sodium channel NaV1.2 are rare with clinically heterogeneous expressions that include epilepsy, autism, and multiple severe to profound impairments and other conditions. To advance understanding of the clinical phenotypes and their relation to channel function, 81 patients (36, 44% female, median age 5.4 years) with 69 unique
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Leptin receptor reactivation restores brain function in early-life Lepr-deficient mice Brain (IF 14.5) Pub Date : 2024-04-23 Caroline Fernandes, Leticia Forny-Germano, Mayara M Andrade, Natalia M Lyra E Silva, Angela M Ramos-Lobo, Fernanda Meireles, Fernanda Tovar-Moll, Jean Christophe Houzel, Jose Donato, Fernanda G De Felice
Obesity is a chronic disease caused by excessive fat accumulation that impacts the body and brain health. Insufficient leptin or leptin receptor (LepR) are involved in the disease pathogenesis. Leptin is involved with several neurological processes, and it has critical developmental roles. We have previously demonstrated that leptin deficiency in early life leads to permanent developmental problems
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Thalamic epileptic spikes disrupt sleep spindles in patients with epileptic encephalopathy Brain (IF 14.5) Pub Date : 2024-04-23 Anirudh Wodeyar, Dhinakaran Chinappen, Dimitris Mylonas, Bryan Baxter, Dara S Manoach, Uri T Eden, Mark A Kramer, Catherine J Chu
In severe epileptic encephalopathies, epileptic activity contributes to progressive cognitive dysfunction. Epileptic encephalopathies share the trait of spike-wave activation during non-rapid eye movement sleep (EE-SWAS), a sleep stage dominated by sleep spindles, brain oscillations known to coordinate offline memory consolidation. Epileptic activity has been proposed to hijack the circuits driving
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Multivariate mapping of low-resilient neurocognitive systems within and around low-grade gliomas Brain (IF 14.5) Pub Date : 2024-04-22 Sam Ng, Sylvie Moritz-Gasser, Anne-Laure Lemaitre, Hugues Duffau, Guillaume Herbet
Accumulating evidence suggests that the brain exhibits a remarkable capacity for functional compensation in response to neurological damage, a resilience potential that is deeply rooted in the malleable features of its underlying anatomo-functional architecture. This propensity is particularly exemplified by diffuse low-grade gliomas (DLGGs), a subtype of primary brain tumour. However, functional plasticity
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Spatial enrichment and genomic analyses reveal the link of NOMO1 with amyotrophic lateral sclerosis Brain (IF 14.5) Pub Date : 2024-04-21 Jingyan Guo, Linya You, Yu Zhou, Jiali Hu, Jiahao Li, Wanli Yang, Xuelin Tang, Yimin Sun, Yuqi Gu, Yi Dong, Xi Chen, Christine Sato, Lorne Zinman, Ekaterina Rogaeva, Jian Wang, Yan Chen, Ming Zhang
Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease with uncertain genetic predisposition in most sporadic cases. Spatial architecture of cell types and gene expression is the basis of cell-cell interactions, biological function and disease pathology, but is not well investigated in human motor cortex, a key ALS relevant brain region. Recent studies indicated single nucleus transcriptomic
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Long-term neuropsychological trajectories in children with epilepsy: does surgery halt decline? Brain (IF 14.5) Pub Date : 2024-04-21 Maria H Eriksson, Freya Prentice, Rory J Piper, Konrad Wagstyl, Sophie Adler, Aswin Chari, John Booth, Friederike Moeller, Krishna Das, Christin Eltze, Gerald Cooray, Ana Perez Caballero, Lara Menzies, Amy McTague, Sara Shavel-Jessop, Martin M Tisdall, J Helen Cross, Patricia Martin Sanfilippo, Torsten Baldeweg
Neuropsychological impairments are common in children with drug-resistant epilepsy. It has been proposed that epilepsy surgery may alleviate these impairments by providing seizure freedom; however, findings from prior studies have been inconsistent. We mapped long-term neuropsychological trajectories in children before and after undergoing epilepsy surgery, to measure the impact of disease course and
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Increased frequency and mortality in persons with neurological disorders during COVID-19 Brain (IF 14.5) Pub Date : 2024-04-18 Candace M Marsters, Jeffrey A Bakal, Grace Y Lam, Finlay A McAlister, Christopher Power
Determining the frequency and outcomes of neurological disorders associated with COVID-19 is imperative for understanding risks as well as recognition of emerging neurological disorders. We investigated the susceptibility and impact of SARS-CoV-2 infection among persons with premorbid neurological disorder rs, as well as the post-infection incidence of neurological sequelae in a case-control population-based
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Different learning aberrations relate to delusion-like beliefs with different contents Brain (IF 14.5) Pub Date : 2024-04-18 Rosa Rossi-Goldthorpe, Steven M Silverstein, James M Gold, Jason Schiffman, James A Waltz, Trevor F Williams, Albert R Powers, Scott W Woods, Richard E Zinbarg, Vijay A Mittal, Lauren M Ellman, Gregory P Strauss, Elaine F Walker, Jason A Levin, Santiago Castiello, Joshua Kenney, Philip R Corlett
The prediction error account of delusions has had success. However, its explanation of delusions with different contents has been lacking. Persecutory delusions and paranoia are the common unfounded beliefs that others have harmful intentions towards us. Other delusions include believing that one’s thoughts or actions are under external control, or that events in the world have specific personal meaning
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Genetics of immune response to Epstein-Barr virus: prospects for multiple sclerosis pathogenesis Brain (IF 14.5) Pub Date : 2024-04-17 Jesse Huang, Katarina Tengvall, Izaura Bomfim Lima, Anna Karin Hedström, Julia Butt, Nicole Brenner, Alexandra Gyllenberg, Pernilla Stridh, Mohsen Khademi, Ingemar Ernberg, Faiez Al Nimer, Ali Manouchehrinia, Jan Hillert, Lars Alfredsson, Oluf Andersen, Peter Sundström, Tim Waterboer, Tomas Olsson, Ingrid Kockum
Epstein-Barr virus (EBV) infection has been advocated as a prerequisite for developing multiple sclerosis (MS) and possibly the propagation of the disease. However, the precise mechanisms for such influences are still unclear. A large-scale study investigating the host genetics of EBV serology and related clinical manifestations, such as infectious mononucleosis (IM), may help us better understand
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Subtitled speech: the neural mechanisms of ticker-tape synaesthesia Brain (IF 14.5) Pub Date : 2024-04-15 Fabien Hauw, Benoît Béranger, Laurent Cohen
Reading acquisition modifies areas of the brain associated with vision, with language, and their connections. Those changes enable reciprocal translation between orthography, and word sounds and meaning. Individual variability in the pre-existing cerebral substrate contributes to the range of eventual reading abilities, extending to atypical developmental patterns, including dyslexia and reading-related
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Adaptive coding of reward in schizophrenia, its change over time and relation to apathy Brain (IF 14.5) Pub Date : 2024-04-12 Mariia Kaliuzhna, Fabien Carruzzo, Noémie Kuenzi, Philippe N Tobler, Matthias Kirschner, Tal Geffen, Teresa Katthagen, Kerem Böge, Marco M Zierhut, Florian Schlagenhauf, Stefan Kaiser
Adaptive coding of reward is the process by which neurons adapt their response to the context of available compensations. Higher rewards lead to a stronger brain response, but the increase of the response depends on the range of available rewards. A steeper increase is observed in a narrow range, and a more gradual slope in a wider range. In schizophrenia, adaptive coding appears affected in different
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Apilimod dimesylate in C9orf72 amyotrophic lateral sclerosis: a randomized phase 2a clinical trial Brain (IF 14.5) Pub Date : 2024-04-09 Suma Babu, Katharine A Nicholson, Jeffrey D Rothstein, Andrea Swenson, Paul J Sampognaro, Pravin Pant, Eric A Macklin, Susan Spruill, Sabrina Paganoni, Tania F Gendron, Mercedes Prudencio, Leonard Petrucelli, Darrell Nix, Sean Landrette, Esther Nkrumah, Keith Fandrick, Joan Edwards, Peter R Young
Apilimod dimesylate is a first-in-class phosphoinositide kinase, FYVE-type zinc finger containing (PIKfyve) inhibitor with favourable clinical safety profile and has demonstrated activity in preclinical C9orf72 and TDP-43 amyotrophic lateral sclerosis models. In this amyotrophic lateral sclerosis clinical trial, the safety, tolerability, CNS penetrance, and modulation of pharmacodynamic target engagement
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GDF5 as a rejuvenating treatment for age-related neuromuscular failure Brain (IF 14.5) Pub Date : 2024-04-08 Traoré Massiré, Noviello Chiara, Vergnol Amélie, Gentil Christel, Halliez Marius, Saillard Lucile, Gelin Maxime, Forand Anne, Lemaitre Mégane, Guesmia Zoheir, Cadot Bruno, Caldas Eriky, Marty Benjamin, Mougenot Nathalie, Messéant Julien, Strochlic Laure, Sadoine Jeremy, Slimani Lofti, Jolly Ariane, De la Grange Pierre, Hogrel Jean-Yves, Pietri-Rouxel France, Falcone Sestina
Sarcopenia involves a progressive loss of skeletal muscle force, quality and mass during ageing, which results in increased inability and death; however, no cure has been established thus far. Growth differentiation factor 5 (GDF5) has been described to modulate muscle mass maintenance in various contexts. For our proof of concept, we overexpressed GDF5 by AAV vector injection in Tibialis Anterior
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More than 185 CAG repeats: a point of no return in Huntington’s disease biology Brain (IF 14.5) Pub Date : 2024-04-08 Jillian Belgrad, Anastasia Khvorova
This scientific commentary refers to ‘A CAG repeat threshold for therapeutics targeting somatic instability in Huntington’s disease’ by Aldous et al. (https://doi.org/10.1093/brain/awae063).
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Neurocomputational model of compulsivity: Deviating from an uncertain goal-directed system Brain (IF 14.5) Pub Date : 2024-04-08 Taekwan Kim, Sang Wan Lee, Silvia Kyungjin Lho, Sun-Young Moon, Minah Kim, Jun Soo Kwon
Despite a theory that an imbalance in goal-directed versus habitual systems serve as building blocks of compulsions, research has yet to delineate how it occurs during an arbitration process between the two systems in obsessive-compulsive disorder. Inspired by a brain model that the inferior frontal cortex selectively gates the putamen to guide goal-directed or habitual actions, this study aimed to
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Tiam1-mediated maladaptive plasticity underlying morphine tolerance and hyperalgesia Brain (IF 14.5) Pub Date : 2024-04-04 Changqun Yao, Xing Fang, Qin Ru, Wei Li, Jun Li, Zeinab Mehsein, Kimberley F Tolias, Lingyong Li
Opioid pain medications, such as morphine, remain the mainstay for treating severe and chronic pain. Prolonged morphine use, however, triggers analgesic tolerance and hyperalgesia (OIH), which can last for a long period after morphine withdrawal. How morphine induces these detrimental side effects remains unclear. Here, we show that morphine tolerance and OIH are mediated by Tiam1-coordinated synaptic
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Functional implication for myelin regeneration in recovery from ischaemic stroke Brain (IF 14.5) Pub Date : 2024-04-04 Stavros Vagionitis, Ragnhildur Thóra Káradóttir
This scientific commentary refers to ‘Prolonged myelin deficits contribute to neuron loss and functional impairments after ischaemic stroke’ by Cheng et al. (https://doi.org/10.1093/brain/awae029).
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Neuroinflammation is a player in coma, but in which role? Brain (IF 14.5) Pub Date : 2024-04-04 Olli Tenovuo, David J Loane
This scientific commentary refers to ‘Neuroimmune activation is associated with neurological outcome in anoxic and traumatic coma’ by Sarton et al. (https://doi.org/10.1093/brain/awae045).
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Preserved striatal innervation maintains motor function despite severe loss of nigral dopaminergic neurons Brain (IF 14.5) Pub Date : 2024-04-04 Thomas Paß, Konrad M Ricke, Pierre Hofmann, Roy S Chowdhury, Yu Nie, Patrick Chinnery, Heike Endepols, Bernd Neumaier, André Carvalho, Lionel Rigoux, Sophie M Steculorum, Julien Prudent, Trine Riemer, Markus Aswendt, Birgit Liss, Bent Brachvogel, Rudolf J Wiesner
Degeneration of dopaminergic neurons in the substantia nigra and their striatal axon terminals causes cardinal motor symptoms of Parkinson’s disease. In idiopathic cases, high levels of mitochondrial DNA alterations leading to mitochondrial dysfunction are a central feature of these vulnerable neurons. Here we present a mouse model expressing the K320E-variant of the mitochondrial helicase Twinkle
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Predictors of cognition after glioma surgery: connectotomy, structure-function phenotype, plasticity Brain (IF 14.5) Pub Date : 2024-04-04 Guillaume Herbet, Hugues Duffau, Emmanuel Mandonnet
Determining preoperatively the maximal extent of resection that would preserve cognitive functions is the core challenge of brain tumor surgery. Over the last decade, the methodological framework to achieve this goal has been thoroughly renewed: the population-level topographically-focused voxel-based lesion-symptom mapping has been progressively overshadowed by machine learning (ML) algorithmics,
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Brain and cognitive changes in patients with long COVID compared with infection-recovered control subjects Brain (IF 14.5) Pub Date : 2024-04-01 Víctor M Serrano del Pueblo, Gemma Serrano-Heras, Carlos M Romero Sánchez, Pepa Piqueras Landete, Laura Rojas-Bartolome, Inmaculada Feria, Richard G M Morris, Bryan Strange, Francisco Mansilla, Linda Zhang, Beatriz Castro-Robles, Lourdes Arias-Salazar, Susana López-López, María Payá, Tomás Segura, Mónica Muñoz-López
Between 2.5 and 28% of people infected with SARS-CoV-2 suffer Long COVID or persistence of symptoms for months after acute illness. Many symptoms are neurological, but the brain changes underlying the neuropsychological impairments remain unclear. This study aimed to provide a detailed description of the cognitive profile, the pattern of brain alterations in Long COVID and the potential association
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Skin keratinocyte-derived SIRT1 and BDNF modulate mechanical allodynia in mouse models of diabetic neuropathy Brain (IF 14.5) Pub Date : 2024-03-30 Jennifer O’Brien, Peter Niehaus, Koping Chang, Juliana Remark, Joy Barrett, Abhishikta Dasgupta, Morayo Adenegan, Mohammad Salimian, Yanni Kevas, Krish Chandrasekaran, Tibor Kristian, Rajeshwari Chellappan, Samuel Rubin, Ashley Kiemen, Catherine Pei-Ju Lu, James W Russell, Cheng-Ying Ho
Diabetic neuropathy is a debilitating disorder characterized by spontaneous and mechanical allodynia. The role of skin mechanoreceptors in the development of mechanical allodynia is unclear. We discovered that mice with diabetic neuropathy had decreased sirtuin 1 (SIRT1) deacetylase activity in foot skin, leading to reduced expression of brain-derived neurotrophic factor (BDNF) and subsequent loss
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Cul-4 inhibition rescues spastin levels and reduces defects in hereditary spastic paraplegia models Brain (IF 14.5) Pub Date : 2024-03-29 Francesca Sardina, Claudia Carsetti, Ludovica Giorgini, Gaia Fattorini, Gianluca Cestra, Cinzia Rinaldo
Hereditary spastic paraplegias (HSPs) are degenerative motor neuron diseases characterized by progressive spasticity and weakness in the lower limbs. The most common form of HSP is due to SPG4 gene haploinsufficiency. SPG4 encodes the microtubule severing enzyme spastin. Although, there is no cure for SPG4-HSP, strategies to induce a spastin recovery are emerging as promising therapeutic approaches
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Central visual pathways affected by degenerative retinal disease before and after gene therapy Brain (IF 14.5) Pub Date : 2024-03-28 Manzar Ashtari, Jean Bennett, David A Leopold
Genetic diseases affecting the retina can result in partial or complete loss of visual function. Leber’s Congenital Amaurosis (LCA) is a rare blinding disease, usually inherited in an autosomally recessive manner, with no cure. Retinal gene therapy has been shown to improve vision in LCA patients caused by mutations in the RPE65 gene (LCA2). However, little is known about how activity in central visual
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Ophthalmate is a new regulator of motor functions via CaSR: Implications for movement disorders Brain (IF 14.5) Pub Date : 2024-03-27 Sammy Alhassen, Derk Hogenkamp, Hung Anh Nguyen, Saeed Al Masri, Geoffrey W Abbott, Olivier Civelli, Amal Alachkar
Dopamine's role as the principal neurotransmitter in motor functions has long been accepted. We broaden this conventional perspective by demonstrating the involvement of non-dopaminergic mechanisms. In mouse models of Parkinson's Disease (PD), we observed that L-DOPA elicited a substantial motor response even when its conversion to dopamine was blocked by inhibiting the enzyme aromatic amino acid decarboxylase
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Brain morphometry in former American football players: Findings from the DIAGNOSE CTE research project Brain (IF 14.5) Pub Date : 2024-03-27 Hector Arciniega, Zachary H Baucom, Fatima Tuz-Zahra, Yorghos Tripodis, Omar John, Holly Carrington, Nicholas Kim, Evdokiya E Knyazhanskaya, Leonard B Jung, Katherine Breedlove, Tim L T Wiegand, Daniel H Daneshvar, R Jarrett Rushmore, Tashrif Billah, Ofer Pasternak, Michael J Coleman, Charles H Adler, Charles Bernick, Laura J Balcer, Michael L Alosco, Inga K Koerte, Alexander P Lin, Jeffrey L Cummings
Exposure to repetitive head impacts (RHIs) in contact sports is associated with neurodegenerative disorders including chronic traumatic encephalopathy (CTE) which currently can be diagnosed only at postmortem. American football players are at higher risk of developing CTE given their exposure to RHIs. One promising approach for diagnosing CTE in vivo is to explore known neuropathological abnormalities
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Reticulon 2 deficiency results in an autosomal recessive distal motor neuropathy with lower limb spasticity Brain (IF 14.5) Pub Date : 2024-03-26 Reza Maroofian, Payam Sarraf, Thomas J O’Brien, Mona Kamel, Arman Cakar, Nour Elkhateeb, Tracy Lau, Siddaramappa Jagdish Patil, Christopher J Record, Alejandro Horga, Miriam Essid, Laila Selim, Hanene Benrhouma, Thouraya Ben Younes, Giovanni Zifarelli, Alistair T Pagnamenta, Peter Bauer, Mukhran Khundadze, Andrea Mirecki, Sara Mahmoud Kamel, Mohamed A Elmonem, Ehsan Ghayoor Karimiani, Yalda Jamshidi
Heterozygous RTN2 variants have been previously identified in a limited cohort of families affected by autosomal dominant spastic paraplegia (SPG12-OMIM:604805) with a variable age of onset. Nevertheless, the definitive validity of SPG12 remains to be confidently confirmed due to scarcity of supporting evidence. In our study, we identified and validated seven novel or ultra-rare homozygous loss-of-function
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Lesion network of oculogyric crises maps to brain dopaminergic transcriptomic signature Brain (IF 14.5) Pub Date : 2024-03-25 Bassam Al-Fatly, Clemens Neudorfer, Diego Kaski, Anthony E Lang, Andrea A Kühn, Michael D Fox, Andreas Horn, Christos Ganos
Oculogyric crises are acute episodes of sustained, typically upward, conjugate deviation of the eyes. Oculogyric crises usually occur as the result of acute D2-dopamine receptor blockade, but the brain areas causally involved in generating this symptom remain elusive. Here, we used data from 14 previously reported cases of lesion-induced oculogyric crises and employed lesion network mapping to identify
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Lucretius and the neural consequences of traumatic amputation: the role of descending inhibition? Brain (IF 14.5) Pub Date : 2024-03-19 Geoffrey D Schott
Geoffrey Schott explores the writings of the Roman poet Lucretius on some of the remarkable phenomena associated with sudden amputation of a limb, and considers what those observations can tell us about the brain mechanisms that might underpin those phenomena.
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A direct spinal cord–computer interface enables the control of the paralysed hand in spinal cord injury Brain (IF 14.5) Pub Date : 2024-03-19 Daniela Souza Oliveira, Matthias Ponfick, Dominik I Braun, Marius Osswald, Marek Sierotowicz, Satyaki Chatterjee, Douglas Weber, Bjoern Eskofier, Claudio Castellini, Dario Farina, Thomas Mehari Kinfe, Alessandro Del Vecchio
The paralysis of the muscles controlling the hand dramatically limits the quality of life of individuals living with spinal cord injury (SCI). Here, with a non-invasive neural interface, we demonstrate that eight motor complete SCI individuals (C5-C6) are still able to task-modulate in real-time the activity of populations of spinal motor neurons with residual neural pathways. In all SCI participants
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Whole genome sequencing increases the diagnostic rate in Charcot-Marie-Tooth disease Brain (IF 14.5) Pub Date : 2024-03-14 Christopher J Record, Menelaos Pipis, Mariola Skorupinska, Julian Blake, Roy Poh, James M Polke, Kelly Eggleton, Tina Nanji, Stephan Zuchner, Andrea Cortese, Henry Houlden, Alexander M Rossor, Matilde Laura, Mary M Reilly
Charcot-Marie-Tooth disease (CMT) is one of the most common and genetically heterogeneous inherited neurological diseases, with more than 130 disease-causing genes. Whole genome sequencing (WGS) has improved diagnosis across genetic diseases, but the diagnostic impact in CMT is yet to be fully reported. We present the diagnostic results from a single specialist inherited neuropathy centre, including
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Dominant CST3 variants cause adult onset leukodystrophy without amyloid angiopathy Brain (IF 14.5) Pub Date : 2024-03-13 Caroline G Bergner, Marjolein Breur, M Clara Soto-Bernardini, Lisa Schäfer, Julia Lier, Diana Le Duc, Linnaeus Bundalian, Susanna Schubert, David Brenner, Friedmar R Kreuz, Björn Schulte, Quinten Waisfisz, Marianna Bugiani, Wolfgang Köhler, Heinrich Sticht, Rami Abou Jamra, Marjo S van der Knaap
Leukodystrophies are rare genetic white matter disorders that have been regarded as mainly occurring in childhood. Recent years altered this perception, as a growing number of leukodystrophies was described to have an onset at adult ages. Still, many adult patients presenting with white matter changes remain without a specific molecular diagnosis. We describe a novel adult onset leukodystrophy in 16