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Publisher: John Wiley and Sons   (Total: 1589 journals)

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Showing 1 - 200 of 1589 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 12, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 65, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 47, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 52, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 164, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 6, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 7, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 4)
Addiction     Hybrid Journal   (Followers: 35, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 14, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 27, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 51, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 14, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 268, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 7, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 21)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 13)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 10)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 16, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 11, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 3, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 16, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 32, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 33, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 51, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 148, SJR: 0.951, h-index: 61)
American Business Law J.     Hybrid Journal   (Followers: 24, SJR: 0.205, h-index: 17)
American Ethnologist     Hybrid Journal   (Followers: 92, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 29, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 34, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 16, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 6, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 37, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 276, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 17, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 138, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 9, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 18)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 220)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 222, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 41, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 7, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 47, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 1, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 8, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 13)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 25, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 17, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 89, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 49, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 8, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 70, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 206, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 49, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 14, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 36, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 27, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 15, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 25, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 3, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 12, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 245, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 52, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 27, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 15)
Asia & the Pacific Policy Studies     Open Access   (Followers: 16)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 320, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (Followers: 1, SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 8, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 4, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 6, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 2, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 15, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 9, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 6, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 14, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 3, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 47, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 7, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 5, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 31, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 14, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 406, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 5, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 72, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 12, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 21, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 36, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 11, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 5, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 9, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 24, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 10, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 16, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 4, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 41, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 6, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 37, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 44, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 141, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 14, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 20, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 38, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 6, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 243, SJR: 2.083, h-index: 125)

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Journal Cover Annals of Clinical and Translational Neurology
  [1 followers]  Follow
    
  This is an Open Access Journal Open Access journal
   ISSN (Online) 2328-9503
   Published by John Wiley and Sons Homepage  [1589 journals]
  • Xeroderma pigmentosum is a definite cause of Huntington's disease-like
           syndrome

    • Authors: Hector Garcia-Moreno; Hiva Fassihi, Robert P.E. Sarkany, Julie Phukan, Thomas Warner, Alan R. Lehmann, Paola Giunti
      Abstract: Xeroderma pigmentosum is characterized by cutaneous, ophthalmological, and neurological features. Although it is typical of childhood, late presentations can mimic different neurodegenerative conditions. We report two families presenting as Huntington's disease-like syndromes. The first case (group G) presented with neuropsychiatric features, cognitive decline and chorea. Typical lentigines were only noticed after the neurological disease started. The second case (group B) presented adult-onset chorea and neuropsychiatric symptoms after an aggressive ocular melanoma. Xeroderma pigmentosum can manifest as a Huntington's Disease-like syndrome. Classic dermatological and oncological features have to be investigated in choreic patients with negative genetic tests for Huntington's disease-like phenotypes.
      PubDate: 2017-12-04T03:31:05.203918-05:
      DOI: 10.1002/acn3.511
       
  • MRI biomarkers of proximal nerve injury in CIDP

    • Authors: Thorsten Lichtenstein; Alina Sprenger, Kilian Weiss, Karin Slebocki, Barbara Cervantes, Dimitrios Karampinos, David Maintz, Gereon R. Fink, Tobias D. Henning, Helmar C. Lehmann
      Abstract: ObjectiveTo evaluate the utility of nerve diffusion tensor imaging (DTI), nerve cross-sectional area, and muscle magnetic resonance imaging (MRI) multiecho Dixon for assessing proximal nerve injury in chronic inflammatory demyelinating polyneuropathy (CIDP).MethodsIn this prospective observational cohort study, 11 patients with CIDP and 11 healthy controls underwent a multiparametric MRI protocol with DTI of the sciatic nerve and assessment of muscle proton-density fat fraction of the biceps femoris and the quadriceps femoris muscles by multiecho Dixon MRI. Patients were longitudinally evaluated by MRI, clinical examination, and nerve conduction studies at baseline and after 6 months.ResultsIn sciatic nerves of CIDP patients, mean cross-sectional area was significantly higher and fractional anisotropy value was significantly lower, compared to controls. In contrast, muscle proton-density fat fraction was significantly higher in thigh muscles of patients with CIDP, compared to controls. MRI parameters showed high reproducibility at baseline and 6 months.InterpretationAdvanced MRI parameters demonstrate subclinical proximal nerve damage and intramuscular fat accumulation in CIDP. Data suggest DTI and multiecho Dixon MRI might be useful in estimating axonal damage and neurogenic muscle changes in CIDP.
      PubDate: 2017-12-04T02:35:30.907842-05:
      DOI: 10.1002/acn3.502
       
  • Diagnostic Potential of Neural Exosome Cargo as Biomarkers for Acute Brain
           Injury

    • Authors: Laura Goetzl; Nana Merabova, Nune Darbinian, Diana Martirosyan, Erica Poletto, Keri Fugarolas, Ogechukwu Menkiti
      Abstract: ObjectiveNeuronal exosomes purified from peripheral blood samples have been proposed as diagnostic tool in the setting of acute brain injury but never tested clinically. We hypothesized that exosome protein biomarkers would change over time following acute hypoxic brain injury and would predict response to therapy.MethodsSynaptopodin (SYNPO), an actin‐associated protein present in postsynaptic spines, was evaluated as a potential biomarker as well as: synaptophysin, neuron‐specific enolase, and mitochondrial cytochrome c oxidase. A secondary analysis was performed on neonatal samples collected at 8, 10, and 14 h after the initiation of therapeutic‐controlled hypothermia for acute hypoxic–ischemic encephalopathy (n = 14). Neuronal exosomes were purified from serum and protein levels were quantified using standard ELISA methods. The primary study outcomes were length of stay (LOS), discharge on seizure medication (DCMED), and composite neuroimaging score (NIS).ResultsThe slope of change in neuronal exosome SYNPO between 8 and 14 h appeared to be the most promising biomarker for all three clinical study outcomes. SYNPO was highly correlated with LOS (−0.91, P < 0.001). SYNPO increased in 6/8 without DCMED and was worse or neutral in 5/5 with DCMED (P = 0.02). All four neonates with an abnormal NIS had neutral or decreasing SYNPO (P = 0.055). Other candidate biomarkers were not associated with outcomes.InterpretationThis report provides the first clinical evidence that neural exosomes turn over rapidly enough in the peripheral circulation to be used as a “troponin‐like” test following acute brain injury. Optimal sampling and biomarkers likely vary with type of brain injury.
      PubDate: 2017-11-24T09:50:26.539555-05:
      DOI: 10.1002/acn3.499
       
  • Cognitive impairment in epilepsy: the role of reduced network flexibility

    • Authors: Chris Tailby; Magdalena A. Kowalczyk, Graeme D. Jackson
      Abstract: ObjectiveThe dominant model of cognitive impairment in focal epilepsy has emphasised structural bases for cognitive deficits. Current theories of cognition in the healthy brain emphasise the importance of the reweighting of brain network interactions in support of task performance. Here, we explore the hypothesis that cognitive deficits in epilepsy arise through abnormalities of dynamic functional network interactions.MethodWe studied 19 healthy controls and 37 temporal lobe epilepsy (TLE) patients, using a behavioural measure of verbal fluency (the Controlled Oral Word Association Test) and an fMRI verbal fluency paradigm (Orthographic Lexical Retrieval).ResultsBehaviourally, verbal fluency was significantly impaired in TLE. Psychophysiological interaction analyses of the fMRI data, which capture state‐dependent changes in network connectivity, revealed reduced task‐dependent modulations of connectivity from left superior medial frontal cortex to left middle frontal gyrus in TLE patients. Individual differences in verbal fluency among TLE cases was correlated with task‐dependent changes in connectivity from left posterior cingulate to left superior medial frontal cortex, and from left superior medial frontal cortex to a range of right predominant brain areas.InterpretationThese data reveal that the typical pattern of task‐driven shifts in network connectivity is not observed in TLE. Our observations go beyond simple structure‐function associations and suggest that failure of network flexibility can be an important contributor to cognitive impairment in epilepsy.
      PubDate: 2017-11-24T07:55:37.935036-05:
      DOI: 10.1002/acn3.503
       
  • Infectious risk stratification in multiple sclerosis patients receiving
           immunotherapy

    • Authors: Jonas Graf; Verena I. Leussink, Thomas Dehmel, Marius Ringelstein, Norbert Goebels, Ortwin Adams, Colin R. MacKenzie, Clemens Warnke, Torsten Feldt, Anna Lammerskitten, Luisa Klotz, Sven Meuth, Heinz Wiendl, Hans-Peter Hartung, Orhan Aktas, Philipp Albrecht
      Abstract: The increasing number of potent treatments for multiple sclerosis warrants screening for infections. To investigate the prevalence of infections in two independent German patient cohorts with multiple sclerosis/neuromyelitis optica spectrum disorders (NMOSD), we performed a retrospective chart review study of multiple sclerosis/NMOSD patients who underwent testing for infections between 2014 and 2016. We show that 6 out of 80 tested patients (Düsseldorf cohort) and 2 out of 97 tested patients (Münster cohort) had a latent tuberculosis infection; total 3.95%, 95% CI: 2–8%. Our findings suggest that latent tuberculosis infection is frequent (>1%). Screening should be performed before embarking on immunomodulatory therapies to allow treatment and mitigation of the risk of a reactivation.
      PubDate: 2017-11-24T07:42:52.37856-05:0
      DOI: 10.1002/acn3.491
       
  • Birth and death of a phantom

    • Authors: Sebastian Dieguez; Mélanie Kaeser, Camille Roux, Jérôme Cottet, Jean-Marie Annoni, Eric Schmidlin
      Abstract: Patients with supernumerary phantom limb report experiencing an additional limb duplicating its physical counterpart, usually following a stroke with sensorimotor disturbances. Here, we report a short‐lasting case of a right upper supernumerary phantom limb with unusual visuomotor features in a healthy participant during a pure Jacksonian motor seizure unexpectedly induced by continuous Theta‐Burst Stimulation over the left primary motor cortex. Electromyographic correlates of the event followed the phenomenological pattern of sudden appearance and brutal dissolution of the phantom, adding credit to the hypothesis that supernumerary phantom limb results from a dynamic resolution of conflictual multimodal information.
      PubDate: 2017-11-17T00:07:07.902182-05:
      DOI: 10.1002/acn3.495
       
  • Clarion call for histopathological clot analysis in “cryptogenic”
           ischemic stroke: implications for diagnosis and treatment

    • Authors: Sonu Bhaskar; Dennis Cordato, Cecilia Cappelen-Smith, Andrew Cheung, David Ledingham, David Celermajer, Christopher Levi
      Abstract: Diagnosis, treatment, and secondary management of cryptogenic stroke patients pose a formidable challenge. The scenario is further complicated in patients with native and prosthetic valvular heart disease. We present a case study of a 36‐year‐old man who received intravenous thrombolysis (IV‐tPA) and endovascular thrombectomy (EVT) for presumed “cryptogenic” complete middle cerebral artery infarction who made a surprisingly excellent clinical recovery despite poor baseline and postintervention neuroimaging. Retrospective gram stain of his clot confirmed a diagnosis of infective endocarditis. This raises an important issue regarding need for more routine histopathological analysis of clot retrieved after EVT in “cryptogenic” stroke patients particularly those with valvular heart disease.
      PubDate: 2017-11-12T19:15:25.236134-05:
      DOI: 10.1002/acn3.500
       
  • Everolimus for treatment of tuberous sclerosis complex‐associated
           neuropsychiatric disorders

    • Authors: Darcy A. Krueger; Anjali Sadhwani, Anna W. Byars, Petrus J. Vries, David N. Franz, Vicky H. Whittemore, Rajna Filip-Dhima, Donna Murray, Kush Kapur, Mustafa Sahin
      Abstract: ObjectiveTo evaluate if short‐term treatment with everolimus was safe and could improve neurocognition and behavior in children with TSC.MethodsThis was a prospective, double‐blind randomized, placebo‐controlled two‐center phase II study. Participants diagnosed with TSC and age 6–21 years were treated with 4.5 mg/m2 per day of oral everolimus (n = 32) or matching placebo (n = 15) taken once daily for 6 months. For efficacy, a comprehensive neurocognitive and behavioral evaluation battery was performed at baseline, 3 months, and 6 months. For safety, adverse events recorded continuously via patient diary were categorized and graded per NCI Common Toxicity Criteria for Adverse Events, version 3.0 (CTCAE 3.0). Analyses were performed on the intention‐to‐treat population (n = 47).ResultsNearly all assessment measures failed to demonstrate significant differences between the two groups at the end of 6 months. Only one measure each of executive function (Cambridge Neuropsychological Test Automated Battery Stockings of Cambridge) favoring placebo (P = 0.025) and social cognition (Social Responsiveness Scale Social Cognition Subscale) favoring everolimus (P = 0.011) was observed. A total of 473 adverse events (AE) were reported. The average number of total AE per subject was similar for both placebo and everolimus. Most were mild or moderate in severity and serious AE were rare.InterpretationWhile safe, oral everolimus administered once daily for 6 months did not significantly improve neurocognitive functioning or behavior in children with TSC.
      PubDate: 2017-11-12T19:05:23.614081-05:
      DOI: 10.1002/acn3.494
       
  • Rivastigmine decreases brain damage in HIV patients with mild cognitive
           deficits

    • Authors: Gaetano Perrotta; Guillaume Bonnier, Djalel-Eddine Meskaldji, David Romascano, Ruslan Aydarkhanov, Alessandro Daducci, Samanta Simioni, Matthias Cavassini, Melanie Metral, François Lazeyras, Reto Meuli, Gunnar Krueger, Renaud A. Du Pasquier, Cristina Granziera
      Abstract: Rivastigmine has been shown to improve cognition in HIV+ patients with minor neurocognitive disorders; however, the mechanisms underlying such beneficial effect are currently unknown. To assess whether rivastigmine therapy is associated with decreased brain inflammation and damage, we performed T1/T2* relaxometry and magnetization transfer imaging in 17 aviremic HIV+ patients with minor neurocognitive disorders enrolled on a crossed over randomized rivastigmine trial. Rivastigmine therapy was associated with changes in MRI metrics indicating a decrease in brain water content (i.e., edema reabsorption) and/or reduced demyelination/axonal damage. Furthermore, MRI changes correlated with cognitive improvement on rivastigmine therapy.
      PubDate: 2017-11-07T06:17:36.383946-05:
      DOI: 10.1002/acn3.493
       
  • Relationships between grip strength, myotonia, and CTG expansion in
           myotonic dystrophy type 1

    • Authors: Jean-Yves Hogrel; Gwenn Ollivier, Isabelle Ledoux, Luc J. Hébert, Bruno Eymard, Jack Puymirat, Guillaume Bassez
      Abstract: In myotonic dystrophy type 1, several studies have suggested causal relationships between CTG repeat length and the severity of symptoms, such as weakness or myotonia. We aimed to explore these relationships in a large population of 144 DM1 patients. All patients underwent clinical and functional assessments using a standardized test for grip strength and myotonia assessment. Myotonia was assessed using a fully automatic software based on mathematical modeling of relaxation force curve. CTG repeat length was statistically correlated with both myotonia and grip strength, which are two major primary neuromuscular symptoms of DM1 patients. However, these relationships are not clinically meaningful and not predictive at the individual level.
      PubDate: 2017-11-07T06:17:34.125651-05:
      DOI: 10.1002/acn3.496
       
  • Neuropathology of childhood‐onset basal ganglia degeneration caused
           by mutation of VAC14

    • Authors: Chloe Stutterd; Peter Diakumis, Melanie Bahlo, Miriam Fanjul Fernandez, Richard J. Leventer, Martin Delatycki, David Amor, Chung W. Chow, Sarah Stephenson, Miriam H. Meisler, Catriona Mclean, Paul J. Lockhart
      Abstract: ObjectiveTo characterize the clinical features and neuropathology associated with recessive VAC14 mutations.MethodsWhole‐exome sequencing was used to identify the genetic etiology of a rapidly progressive neurological disease presenting in early childhood in two deceased siblings with distinct neuropathological features on post mortem examination.ResultsWe identified compound heterozygous variants in VAC14 in two deceased siblings with early childhood onset of severe, progressive dystonia, and neurodegeneration. Their clinical phenotype is consistent with the VAC14–related childhood‐onset, striatonigral degeneration recently described in two unrelated children. Post mortem examination demonstrated prominent vacuolation associated with degenerating neurons in the caudate nucleus, putamen, and globus pallidus, similar to previously reported ex vivo vacuoles seen in the late‐endosome/lysosome of VAC14‐deficient neurons. We identified upregulation of ubiquitinated granules within the cell cytoplasm and lysosomal‐associated membrane protein (LAMP2) around the vacuole edge to suggest a process of vacuolation of lysosomal structures associated with active autophagocytic‐associated neuronal degeneration.InterpretationOur findings reveal a distinct clinicopathological phenotype associated with recessive VAC14 mutations.
      PubDate: 2017-11-07T06:17:32.111275-05:
      DOI: 10.1002/acn3.487
       
  • Flupirtine and diazepam combination terminates established status
           epilepticus: results in three rodent models

    • Authors: Terry Zhang; Marko S. Todorovic, John Williamson, Jaideep Kapur
      Abstract: ObjectiveStatus epilepticus (SE) is a neurological emergency requiring rapid termination of seizures. New treatment choices are needed for benzodiazepine‐refractory SE or established SE (ESE). Previous studies have demonstrated that the potassium‐channel opener flupirtine terminates seizures in neonatal animals. However, its effectiveness in adult ESE has not been tested. We tested whether flupirtine alone or in combination with the benzodiazepine diazepam would terminate ESE in three animal models.MethodsSE was induced by administration of lithium followed by pilocarpine, by electrical stimulation of the hippocampus or by diisopropylfluorophosphate (DFP) administration. Seizures were assessed by EEG recorded from the hippocampus and cortex.ResultsFlupirtine alone did not terminate ESE within 60 min of administration in any of the three models of ESE. A combination of flupirtine and diazepam terminated ESE within 60 min in all the three models. The drug combination shortened the duration of ESE in all three models. Drug responsiveness was distinct between each model.ConclusionA combination of the potassium channel opener flupirtine and diazepam is a potential therapy for ESE.
      PubDate: 2017-11-07T06:17:14.858417-05:
      DOI: 10.1002/acn3.497
       
  • mGluR2/3 activation of the SIRT1 axis preserves mitochondrial function in
           diabetic neuropathy

    • Authors: Krish Chandrasekaran; Anjaneyulu Muragundla, Tyler G. Demarest, Joungil Choi, Avinash R. Sagi, Neda Najimi, Pranith Kumar, Anmol Singh, Cheng-Ying Ho, Gary Fiskum, Lauren G. Koch, Steven L. Britton, James W. Russell
      Abstract: ObjectivesThere is a critical need to develop effective treatments for diabetic neuropathy. This study determined if a selective mGluR2/3 receptor agonist prevented or treated experimental diabetic peripheral neuropathy (DPN) through glutamate recycling and improved mitochondrial function.MethodsAdult male streptozotocin treated Sprague‐Dawley rats with features of type 1 diabetes mellitus (T1DM) or Low Capacity Running (LCR) rats with insulin resistance or glucose intolerance were treated with 3 or 10 mg/kg/day LY379268. Neuropathy end points included mechanical allodynia, nerve conduction velocities (NCV), and intraepidermal nerve fiber density (IENFD). Markers of oxidative stress, antioxidant response, glutamate recycling pathways, and mitochondrial oxidative phosphorylation (OXPHOS) associated proteins were measured in dorsal root ganglia (DRG).ResultsIn diabetic rats, NCV and IENFD were decreased. Diabetic rats treated with an mGluR2/3 agonist did not develop neuropathy despite remaining diabetic. Diabetic DRG showed increased levels of oxidized proteins, decreased levels of glutathione, decreased levels of mitochondrial DNA (mtDNA) and OXPHOS proteins. In addition, there was a 20‐fold increase in levels of glial fibrillary acidic protein (GFAP) and the levels of glutamine synthetase and glutamate transporter proteins were decreased. When treated with a specific mGluR2/3 agonist, levels of glutathione, GFAP and oxidized proteins were normalized and levels of superoxide dismutase 2 (SOD2), SIRT1, PGC‐1α, TFAM, glutamate transporter proteins, and glutamine synthetase were increased in DRG neurons.InterpretationActivation of glutamate recycling pathways protects diabetic DRG and this is associated with activation of the SIRT1‐PGC‐1α–TFAM axis and preservation of mitochondrial OXPHOS function.
      PubDate: 2017-11-01T23:47:45.581192-05:
      DOI: 10.1002/acn3.484
       
  • Minocycline protects against delayed cerebral ischemia after subarachnoid
           hemorrhage via matrix metalloproteinase‐9 inhibition

    • Authors: Ananth K. Vellimana; Meng-Liang Zhou, Itender Singh, Diane J. Aum, James W. Nelson, Glenn R. Harris, Umeshkumar Athiraman, Byung H. Han, Gregory J. Zipfel
      Abstract: ObjectiveDelayed cerebral ischemia (DCI) is an independent risk factor for poor outcome after aneurysmal subarachnoid hemorrhage (SAH) and is multifactorial in etiology. While prior studies have suggested a role for matrix metalloproteinase‐9 (MMP‐9) in early brain injury after SAH, its contribution to the pathophysiology of DCI is unclear.MethodsIn the first experiment, wild‐type (WT) and MMP‐9−/− mice were subjected to sham or endovascular perforation SAH surgery. In separate experiments, WT and MMP‐9−/−mice were administered vehicle or minocycline either pre‐ or post‐SAH. All mice underwent assessment of multiple components of DCI including vasospasm, neurobehavioral function, and microvessel thrombosis. In another experiment, rabbits were subjected to sham or cisterna magna injection SAH surgery, and administered vehicle or minocycline followed by vasospasm assessment.ResultsMMP‐9 expression and activity was increased after SAH. Genetic (MMP‐9−/− mice) and pharmacological (pre‐SAH minocycline administration) inhibition of MMP‐9 resulted in decreased vasospasm and neurobehavioral deficits. A therapeutically feasible strategy of post‐SAH administration of minocycline resulted in attenuation of multiple components of DCI. Minocycline administration to MMP‐9−/− mice did not yield additional protection. Consistent with experiments in mice, both pre‐ and post‐SAH administration of minocycline attenuated SAH‐induced vasospasm in rabbits.InterpretationMMP‐9 is a key player in the pathogenesis of DCI. The consistent attenuation of multiple components of DCI with both pre‐ and post‐SAH administration of minocycline across different species and experimental models of SAH, combined with the excellent safety profile of minocycline in humans suggest that a clinical trial in SAH patients is warranted.
      PubDate: 2017-10-30T08:06:57.440317-05:
      DOI: 10.1002/acn3.492
       
  • Efficacy and safety of anti‐amyloid‐β immunotherapy for Alzheimer's
           disease: a systematic review and network meta‐analysis

    • Authors: Jia-Jie Mo; Jin-yu Li, Zheng Yang, Zhou Liu, Jin-Shan Feng
      Abstract: To review the optimality and safety of different anti‐Amyloid‐β(Aβ) immunotherapies for Alzheimer's disease (AD). Published randomized controlled trials were comprehensively reviewed from electronic databases (Cochrane library, Embase, Pubmed, and Google scholar). Pooled outcomes as mean difference or odds ratio values with 95% confidence interval were reported. The network estimates with confidence and predictive intervals for all pairwise relative effects was evaluated. Optimal intervention was ranked by benefit‐risk ratio based on the surface under the cumulative ranking curve. Eleven eligible RCTs from 9 literatures, including 5141 patients and 5 interventions were included. The quality of evidence was rated low in comparisons. For efficacy, in terms of Mini‐Mental State Examination, aducanumab and solanezumab are significantly effective than placebo. For safety, in terms of Amyloid‐Related Imaging Abnormalities (ARIA), bapineuzumab and aducanumab are significantly worse than placebo. There were no significant differences in outcomes of Alzheimer's disease Assessment Scale‐Cognitive subscale, Disability Assessment for Dementia, Adverse Events, and mortality. Given the clinical therapeutic effects of anti‐Aβ immunotherapies for AD, aducanumab and solanezumab improve the cognitive function, while aducanumab and bapineuzumab may increase the risks of ARIA.
      PubDate: 2017-10-30T07:51:08.079406-05:
      DOI: 10.1002/acn3.469
       
  • Lateral hypothalamic activity indicates hunger and satiety states in
           humans

    • Authors: Omid Talakoub; Raquel R. Paiva, Matija Milosevic, Marcelo Q. Hoexter, Ruth Franco, Eduardo Alho, Jessie Navarro, José F. Pereira, Milos R. Popovic, Cary Savage, Antonio C. Lopes, Pedro Alvarenga, Durval Damiani, Manoel J. Teixeira, Euripides C. Miguel, Erich T. Fonoff, Marcelo C. Batistuzzo, Clement Hamani
      Abstract: Lateral hypothalamic area (LHA) local field potentials (LFPs) were recorded in a Prader–Willi patient undergoing deep brain stimulation (DBS) for obesity. During hunger, exposure to food‐related cues induced an increase in beta/low‐gamma activity. In contrast, recordings during satiety were marked by prominent alpha rhythms. Based on these findings, we have delivered alpha‐frequency DBS prior to and during food intake. Despite reporting an early sensation of fullness, the patient continued to crave food. This suggests that the pattern of activity in LHA may indicate hunger/satiety states in humans but attest to the complexity of conducting neuromodulation studies in obesity.
      PubDate: 2017-10-20T23:05:59.964959-05:
      DOI: 10.1002/acn3.466
       
  • 4‐Hydroxybenzoic acid restores CoQ10 biosynthesis in human COQ2
           deficiency

    • Authors: Diran Herebian; Annette Seibt, Sander H. J. Smits, Richard J. Rodenburg, Ertan Mayatepek, Felix Distelmaier
      Abstract: The clinical phenotypes of human CoQ10‐deficiency caused by COQ2 mutations range from fatal neonatal disease to adult‐onset multisystem atrophy. So far, treatment options for these diseases are unsatisfactory. Here, we demonstrate that supplementation of 4‐hydroxybenzoic acid (4‐HBA) fully restores endogenous CoQ10‐biosynthesis in COQ2‐deficient cell lines. This was accompanied by increased protein expression of CoQ10‐biosynthesis‐enzymes as well as a rescue of cell viability during stress conditions. In silico analysis suggested a ligand transportation path for 4‐HBA through the COQ2 protein towards the mitochondrial matrix side. This process is apparently hindered by disease‐causing mutations, which can be overcome by increasing 4‐HBA concentrations.
      PubDate: 2017-10-17T07:22:16.093677-05:
      DOI: 10.1002/acn3.486
       
  • Issue Information

    • First page: 765
      PubDate: 2017-11-12T18:31:21.641214-05:
      DOI: 10.1002/acn3.359
       
  • NMDAR encephalitis: passive transfer from man to mouse by a recombinant
           antibody

    • Authors: Manish Malviya; Sumanta Barman, Kristin S. Golombeck, Jesús Planagumà, Francesco Mannara, Nathalie Strutz-Seebohm, Claudia Wrzos, Fatih Demir, Christine Baksmeier, Julia Steckel, Kim Kristin Falk, Catharina C. Gross, Stjepana Kovac, Kathrin Bönte, Andreas Johnen, Klaus-Peter Wandinger, Elena Martín-García, Albert J. Becker, Christian E. Elger, Nikolaj Klöcker, Heinz Wiendl, Sven G. Meuth, Hans-Peter Hartung, Guiscard Seebohm, Frank Leypoldt, Rafael Maldonado, Christine Stadelmann, Josep Dalmau, Nico Melzer, Norbert Goebels
      First page: 768
      Abstract: ObjectiveAutoimmune encephalitis is most frequently associated with anti‐NMDAR autoantibodies. Their pathogenic relevance has been suggested by passive transfer of patients' cerebrospinal fluid (CSF) in mice in vivo. We aimed to analyze the intrathecal plasma cell repertoire, identify autoantibody‐producing clones, and characterize their antibody signatures in recombinant form.MethodsPatients with recent onset typical anti‐NMDAR encephalitis were subjected to flow cytometry analysis of the peripheral and intrathecal immune response before, during, and after immunotherapy. Recombinant human monoclonal antibodies (rhuMab) were cloned and expressed from matching immunoglobulin heavy‐ (IgH) and light‐chain (IgL) amplicons of clonally expanded intrathecal plasma cells (cePc) and tested for their pathogenic relevance.ResultsIntrathecal accumulation of B and plasma cells corresponded to the clinical course. The presence of cePc with hypermutated antigen receptors indicated an antigen‐driven intrathecal immune response. Consistently, a single recombinant human GluN1‐specific monoclonal antibody, rebuilt from intrathecal cePc, was sufficient to reproduce NMDAR epitope specificity in vitro. After intraventricular infusion in mice, it accumulated in the hippocampus, decreased synaptic NMDAR density, and caused severe reversible memory impairment, a key pathogenic feature of the human disease, in vivo.InterpretationA CNS‐specific humoral immune response is present in anti‐NMDAR encephalitis specifically targeting the GluN1 subunit of the NMDAR. Using reverse genetics, we recovered the typical intrathecal antibody signature in recombinant form, and proved its pathogenic relevance by passive transfer of disease symptoms from man to mouse, providing the critical link between intrathecal immune response and the pathogenesis of anti‐NMDAR encephalitis as a humorally mediated autoimmune disease.
      PubDate: 2017-10-03T23:06:42.940989-05:
      DOI: 10.1002/acn3.444
       
  • Divergent neural responses to narrative speech in disorders of
           consciousness

    • Authors: Ivan Iotzov; Brian C. Fidali, Agustin Petroni, Mary M. Conte, Nicholas D. Schiff, Lucas C. Parra
      First page: 784
      Abstract: ObjectiveClinical assessment of auditory attention in patients with disorders of consciousness is often limited by motor impairment. Here, we employ intersubject correlations among electroencephalography responses to naturalistic speech in order to assay auditory attention among patients and healthy controls.MethodsElectroencephalographic data were recorded from 20 subjects with disorders of consciousness and 14 healthy controls during of two narrative audio stimuli, presented both forwards and time‐reversed. Intersubject correlation of evoked electroencephalography signals were calculated, comparing responses of both groups to those of the healthy control subjects. This analysis was performed blinded and subsequently compared to the diagnostic status of each patient based on the Coma Recovery Scale‐Revised.ResultsSubjects with disorders of consciousness exhibit significantly lower intersubject correlation than healthy controls during narrative speech. Additionally, while healthy subjects had higher intersubject correlation values in forwards versus backwards presentation, neural responses did not vary significantly with the direction of playback in subjects with disorders of consciousness. Increased intersubject correlation values in the backward speech condition were noted with improving disorder of consciousness diagnosis, both in cross‐sectional analysis and in a subset of patients with longitudinal data.InterpretationIntersubject correlation of neural responses to narrative speech audition differentiates healthy controls from patients and appears to index clinical diagnoses in disorders of consciousness.
      PubDate: 2017-09-27T23:05:30.801631-05:
      DOI: 10.1002/acn3.470
       
  • Soluble CD163 in intracerebral hemorrhage: biomarker for perihematomal
           edema

    • Authors: Meaghan Roy-O'Reilly; Liang Zhu, Louise Atadja, Glenda Torres, Jaroslaw Aronowski, Louise McCullough, Nancy J. Edwards
      First page: 793
      Abstract: ObjectivePatients with intracerebral hemorrhage (ICH) may elaborate varying degrees of perihematomal edema (PHE), requiring closer monitoring and a higher intensity of treatment. Here, we explore whether the soluble form of CD163, a scavenger receptor responsible for hemoglobin sequestration, can serve as a prognostic biomarker of PHE development and poor outcome after ICH.MethodsOur study cohort was comprised of 51 primary age‐ and sex‐matched ICH patients with moderate‐sized, hypertensive deep hemorrhages. Patients were part of a prospective ICH registry cataloguing admission data along with functional outcomes. We measured sCD163 levels in serial serum and cerebrospinal fluid (CSF) samples obtained at prespecified timepoints. Descriptive statistics, including a generalized estimating equation for longitudinal data, were used to analyze sCD163 in relation to ICH outcomes.ResultsAcute serum sCD163 (
      PubDate: 2017-10-19T20:55:30.39497-05:0
      DOI: 10.1002/acn3.485
       
  • Sex differences in LRRK2 G2019S and idiopathic Parkinson's Disease

    • Authors: Marta San Luciano; Cuiling Wang, Roberto A. Ortega, Nir Giladi, Karen Marder, Susan Bressman, Rachel Saunders-Pullman,
      First page: 801
      Abstract: ObjectiveTo evaluate sex differences and the relative effect of G2019S LRRK2 mutations in Parkinson's disease (PD).Methods530 LRRK2 PD carriers and 759 noncarrier PD (idiopathic, IPD) evaluated as part of the Fox Foundation (MJFF) Consortium were included. All participants completed a study visit including information on clinical features, treatment, examination, and motor and nonmotor questionnaires. Clinical features were compared between men and women separately for IPD and LRRK2 PD; and features were compared between IPD and LRRK2 PD separately for men and women.ResultsAmong IPD: men had higher levodopa equivalency dose (LED), worse activities of daily living and motoric severity but lower complications of therapy (UPDRS‐IV). IPD women had higher olfaction and thermoregulatory scores and were more likely to report family history of PD. Among LRRK2 PD: Male predominance was not observed among G2019S LRRK2 cases. Women had worse UPDRS‐IV but better olfaction. Among same sex: LRRK2 men and women had better olfaction than IPD counterparts. LRRK2 men demonstrated lower motor and higher cognitive, RBD and thermoregulation scores than IPD men and LRRK2 women had greater UDPRS‐IV and rates of dyskinesia.InterpretationThere were clinical differences between sexes with a more severe phenotype in IPD men and more complications of therapy in women. The more severe male phenotype was moderated by LRRK2, with LRRK2 men and women showing less diversity of phenotype. Our study supports that both genetics and sex drive phenotype, and thus trials in LRRK2 and IPD should consider gender stratification in design or analysis.
      PubDate: 2017-10-19T20:40:37.042756-05:
      DOI: 10.1002/acn3.489
       
  • PREP2: A biomarker‐based algorithm for predicting upper limb
           function after stroke

    • Authors: Cathy M. Stinear; Winston D. Byblow, Suzanne J. Ackerley, Marie-Claire Smith, Victor M. Borges, P. Alan Barber
      First page: 811
      Abstract: ObjectiveRecovery of motor function is important for regaining independence after stroke, but difficult to predict for individual patients. Our aim was to develop an efficient, accurate, and accessible algorithm for use in clinical settings. Clinical, neurophysiological, and neuroimaging biomarkers of corticospinal integrity obtained within days of stroke were combined to predict likely upper limb motor outcomes 3 months after stroke.MethodsData from 207 patients recruited within 3 days of stroke [103 females (50%), median age 72 (range 18–98) years] were included in a Classification and Regression Tree analysis to predict upper limb function 3 months poststroke.ResultsThe analysis produced an algorithm that sequentially combined a measure of upper limb impairment; age; the presence or absence of upper limb motor evoked potentials elicited with transcranial magnetic stimulation; and stroke lesion load obtained from MRI or stroke severity assessed with the NIHSS score. The algorithm makes correct predictions for 75% of patients. A key biomarker obtained with transcranial magnetic stimulation is required for one third of patients. This biomarker combined with NIHSS score can be used in place of more costly magnetic resonance imaging, with no loss of prediction accuracy.InterpretationThe new algorithm is more accurate, efficient, and accessible than its predecessors, which may support its use in clinical practice. While further work is needed to potentially incorporate sensory and cognitive factors, the algorithm can be used within days of stroke to provide accurate predictions of upper limb functional outcomes at 3 months after stroke. www.presto.auckland.ac.nz
      PubDate: 2017-10-24T06:33:05.649375-05:
      DOI: 10.1002/acn3.488
       
  • Multigeneration family with dominant SPG30 hereditary spastic paraplegia

    • Authors: Ricardo H. Roda; Alice B. Schindler, Craig Blackstone
      First page: 821
      Abstract: Autosomal recessive KIF1A missense mutations cause hereditary spastic paraplegia (HSP) type SPG30, while recessive truncations lead to sensory and autonomic neuropathy (HSN2C) and many de novo missense mutations are associated with cognitive impairment. Here, we describe family members across three generations with pure HSP. A heterozygous p.Ser69Leu KIF1A mutation segregates with those afflicted. The same variant was previously reported in a Finnish father and son with pure HSP as well as four members of a Sicilian kindred with more intrafamilial phenotypic variability. This further validates the pathogenicity of the p.Ser69Leu mutation and suggests that it may represent a mutation hot spot.
      PubDate: 2017-10-14T23:05:45.450453-05:
      DOI: 10.1002/acn3.452
       
  • CD4+ T cells from multiple sclerosis patients respond to a
           commensal‐derived antigen

    • Authors: Joseph N. Burgess; Anudeep B. Pant, Lloyd H. Kasper, Sara Colpitts Brass
      First page: 825
      Abstract: Multiple sclerosis, an immune‐mediated disease of the central nervous system, is characterized by the impaired function of regulatory cells that fail to suppress self‐reactive effector cells. We have previously found that polysaccharide A, a capsular antigen derived from the human gut commensal Bacteroides fragilis, can induce a population of regulatory T cells. Herein, we demonstrate that naïve T cells isolated from patients with multiple sclerosis have the capacity to acquire regulatory characteristics when stimulated in vitro with polysaccharide A. This study demonstrates the amplification of a regulatory T cell response by a gut‐derived commensal antigen in those with multiple sclerosis.
      PubDate: 2017-09-27T09:47:00.175235-05:
      DOI: 10.1002/acn3.465
       
  • Botulinum toxin treatment for hypersalivation in anti‐NMDA receptor
           encephalitis

    • Authors: Jin-Sun Jun; Han Gil Seo, Soon-Tae Lee, Kon Chu, Sang Kun Lee
      First page: 830
      Abstract: Hypersalivation is one of the intractable symptoms of anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis. While anticholinergic medications partially improve the hypersalivation, they can aggravate the autonomic dysfunctions associated with anti‐NMDAR encephalitis. Thus, we investigated the efficacy and safety of botulinum toxin type A injection on hypersalivation refractory to anticholinergics in six patients with anti‐NMDAR encephalitis. Hypersalivation was well‐controlled without remarkable adverse reaction over 16 weeks after botulinum toxin type A, although two patients were reinjected at 12 weeks due to reaggravation of hypersalivation. Our findings suggest that botulinum toxin type A might be a better choice than anticholinergics for management of hypersalivation in patients with anti‐NMDAR encephalitis.
      PubDate: 2017-09-26T02:30:26.454134-05:
      DOI: 10.1002/acn3.467
       
  • Donepezil enhances understanding of degraded speech in Alzheimer's disease

    • Authors: Chris J. D. Hardy; Yun T. Hwang, Rebecca L. Bond, Charles R. Marshall, Basil H. Ridha, Sebastian J. Crutch, Martin N. Rossor, Jason D. Warren
      First page: 835
      Abstract: Auditory dysfunction under complex, dynamic listening conditions is a clinical hallmark of Alzheimer's disease (AD) but challenging to measure and manage. Here, we assessed understanding of sinewave speech (a paradigm of degraded speech perception) and general cognitive abilities in 17 AD patients, before and following a 10 mg dose of donepezil. Relative to healthy older individuals, patients had impaired sinewave speech comprehension that was selectively ameliorated by donepezil. Our findings demonstrate impaired perception of degraded speech in AD but retained perceptual learning capacity that can be harnessed by acetylcholinesterase inhibition, with implications for designing communication interventions and acoustic environments in dementia.
      PubDate: 2017-09-27T09:56:04.841966-05:
      DOI: 10.1002/acn3.471
       
 
 
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