WashU weekly Neuroscience publications

Molecular classification of a complex structural rearrangement of the RB1 locus in an infant with sporadic, isolated, intracranial, sellar region retinoblastoma
(2021) Acta Neuropathologica Communications, 9 (1), art. no. 61, . 

Schieffer, K.M.^a , Feldman, A.Z.^b , Kautto, E.A.^a , McGrath, S.^a , Miller, A.R.^a , Hernandez-Gonzalez, M.E.^a , LaHaye, S.^a , Miller, K.E.^a , Koboldt, D.C.^a c , Brennan, P.^a , Kelly, B.^a , Wetzel, A.^a , Agarwal, V.^d , Shatara, M.^e , Conley, S.^f , Rodriguez, D.P.^g , Abu-Arja, R.^f , Shaikhkhalil, A.^h , Snuderl, M.ⁱ , Orr, B.A.^j , Finlay, J.L.^f k l , Osorio, D.S.^c f k , Drapeau, A.I.^m n , Leonard, J.R.^m n , Pierson, C.R.^o p q , White, P.^a c , Magrini, V.^a c , Mardis, E.R.^a c n , Wilson, R.K.^a c , Cottrell, C.E.^a c p , Boué, D.R.^o p

^a The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute At Nationwide Children’s Hospital, 575 Children’s Crossroad, Columbus, OH 43215, United States
^b Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
^c Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United States
^d Division of Hematology/Oncology, Department of Pediatrics, Nemours Children’s Health System, Orlando, FL, United States
^e Division of Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
^f Division of Hematology, Oncology, and Bone Marrow Transplant, Nationwide Children’s Hospital, Columbus, OH, United States
^g Department of Radiology, Nationwide Children’s Hospital, Columbus, OH, United States
^h Division of Gastroenterology & Hepatology & Nutrition, Nationwide Children’s Hospital, Columbus, OH, United States
ⁱ Department of Pathology, New York University Langone Health, New York City, NY, United States
^j Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, United States
^k Division of Hematology and Oncology, The Ohio State University College of Medicine, Columbus, OH, United States
^l Departments of Pediatrics and Radiation Oncology, The Ohio State University College of Medicine, Columbus, OH, United States
^m Division of Neurosurgery, Nationwide Children’s Hospital, Columbus, OH, United States
ⁿ Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH, United States
^o Department of Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH, United States
^p Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, United States
^q Department of Biomedical Education & Anatomy, The Ohio State University, Columbus, OH, United States

Abstract
Retinoblastoma is a childhood cancer of the retina involving germline or somatic alterations of the RB Transcriptional Corepressor 1 gene, RB1. Rare cases of sellar-suprasellar region retinoblastoma without evidence of ocular or pineal tumors have been described. A nine-month-old male presented with a sellar-suprasellar region mass. Histopathology showed an embryonal tumor with focal Flexner-Wintersteiner-like rosettes and loss of retinoblastoma protein (RB1) expression by immunohistochemistry. DNA array-based methylation profiling confidently classified the tumor as pineoblastoma group A/intracranial retinoblastoma. The patient was subsequently enrolled on an institutional translational cancer research protocol and underwent comprehensive molecular profiling, including paired tumor/normal exome and genome sequencing and RNA-sequencing of the tumor. Additionally, Pacific Biosciences (PacBio) Single Molecule Real Time (SMRT) sequencing was performed from comparator normal and disease-involved tissue to resolve complex structural variations. RNA-sequencing revealed multiple fusions clustered within 13q14.1-q21.3, including a novel in-frame fusion of RB1-SIAH3 predicted to prematurely truncate the RB1 protein. SMRT sequencing revealed a complex structural rearrangement spanning 13q14.11-q31.3, including two somatic structural variants within intron 17 of RB1. These events corresponded to the RB1-SIAH3 fusion and a novel RB1 rearrangement expected to correlate with the complete absence of RB1 protein expression. Comprehensive molecular analysis, including DNA array-based methylation profiling and sequencing-based methodologies, were critical for classification and understanding the complex mechanism of RB1 inactivation in this diagnostically challenging tumor. © 2021, The Author(s).

Author Keywords
DNA array-based methylation;  Intracranial retinoblastoma;  PacBio;  RB1;  Sellar-suprasellar retinoblastoma;  SMRT sequencing;  Structural variation

Funding details
National Institutes of HealthNIH2T32GM068412-11A1
National Institute of General Medical SciencesNIGMS

Multicentric tracking of multiple agents by anterior cingulate cortex during pursuit and evasion
(2021) Nature Communications, 12 (1), art. no. 1985, . 

Yoo, S.B.M.^a b c d , Tu, J.C.^a e , Hayden, B.Y.^a

^a Department of Neuroscience, Center for Magnetic Resonance Research, and Center for Neuroengineering, University of Minnesota, Minneapolis, MN, United States
^b Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, South Korea
^c Department of Biomedical Engineering, Sungkyunkwan University, Suwon, South Korea
^d Department of Brain and Cognitive Sciences, Massachusetts Institution of Technology, Cambridge, MA, United States
^e Department of Neuroscience, Washington University at St.Louis, St.Louis, MO, United States

Abstract
Successful pursuit and evasion require rapid and precise coordination of navigation with adaptive motor control. We hypothesize that the dorsal anterior cingulate cortex (dACC), which communicates bidirectionally with both the hippocampal complex and premotor/motor areas, would serve a mapping role in this process. We recorded responses of dACC ensembles in two macaques performing a joystick-controlled continuous pursuit/evasion task. We find that dACC carries two sets of signals, (1) world-centric variables that together form a representation of the position and velocity of all relevant agents (self, prey, and predator) in the virtual world, and (2) avatar-centric variables, i.e. self-prey distance and angle. Both sets of variables are multiplexed within an overlapping set of neurons. Our results suggest that dACC may contribute to pursuit and evasion by computing and continuously updating a multicentric representation of the unfolding task state, and support the hypothesis that it plays a high-level abstract role in the control of behavior. © 2021, The Author(s).

Vitamin A1/A2 chromophore exchange: Its role in spectral tuning and visual plasticity
(2021) Developmental Biology, 475, pp. 145-155. 

Corbo, J.C.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, 63110, United States

Abstract
Vertebrate rod and cone photoreceptors detect light via a specialized organelle called the outer segment. This structure is packed with light-sensitive molecules known as visual pigments that consist of a G-protein-coupled, seven-transmembrane protein known as opsin, and a chromophore prosthetic group, either 11-cis retinal (‘A1’) or 11-cis 3,4-didehydroretinal (‘A2’). The enzyme cyp27c1 converts A1 into A2 in the retinal pigment epithelium. Replacing A1 with A2 in a visual pigment red-shifts its spectral sensitivity and broadens its bandwidth of absorption at the expense of decreased photosensitivity and increased thermal noise. The use of vitamin A2-based visual pigments is strongly associated with the occupation of aquatic habitats in which the ambient light is red-shifted. By modulating the A1/A2 ratio in the retina, an organism can dynamically tune the spectral sensitivity of the visual system to better match the predominant wavelengths of light in its environment. As many as a quarter of all vertebrate species utilize A2, at least during a part of their life cycle or under certain environmental conditions. A2 utilization therefore represents an important and widespread mechanism of sensory plasticity. This review provides an up-to-date account of the A1/A2 chromophore exchange system. © 2021

Author Keywords
Chromophore;  Cones;  Opsins;  Photoreceptors;  Porphyropsin;  Retina;  Rods;  Sensory plasticity;  Spectral tuning;  Visual ecology;  Visual pigments;  Visual plasticity;  Vitamin A1;  Vitamin A2

Funding details
National Institutes of HealthNIHEY025196, EY026672, EY030075

White matter abnormalities of right hemisphere attention networks contribute to visual hallucinations in dementia with Lewy bodies
(2021) Cortex, 139, pp. 86-98. 

Zorzi, G.^a b , Thiebaut de Schotten, M.^b c d , Manara, R.^a b , Bussè, C.^a , Corbetta, M.^a b e , Cagnin, A.^a b

^a Department of Neuroscience, University of Padova, Padova, Italy
^b Padova Neuroscience Center, University of Padova, Padova, Italy
^c Brain Connectivity and Behaviour Laboratory, Sorbonne Universities, Paris, France
^d Groupe d’Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives-UMR 5293, CNRS, CEA University of Bordeaux, Bordeaux, France
^e Department of Neurology, Radiology, Neuroscience, Washington University School of Medicine, St.Louis, MO, United States

Abstract
Objective: Functional alterations of the visual attention networks in a setting of impaired visual information processing have a role in the genesis of visual hallucinations (VH) in dementia with Lewy bodies (DLB). This multimodal MRI study aims at exploring structural and functional basis of VH. Methods: 23 DLB patients (10 with and 13 without VH) and 13 healthy controls were studied. They underwent MRI with T1-w sequences to measure cortical thickness, DTI for whole-brain and single tract microstructural properties and rs-fMRI of the default mode, dorsal and ventral attention, and visual networks. Results: In DLB with VH, whole-brain DTI revealed a lower fractional anisotropy and a greater mean diffusivity in the right frontal and temporo-parietal white matter tracts. Tracts dissection showed lower fractional anisotropy in the right inferior and superior (ventral part) longitudinal fasciculi (ILF and SLF) (p <.05, corrected), and greater mean diffusivity (p <.05). The extent of white matter microstructural alterations involving the right ILF and SLF correlated with the severity of VH (r =.55, p <.01; r =.42, p <.05, respectively), and with performance in the visual attention task (r = −.56 and r = −.61; p <.01, respectively). Cortical thickness in the projection areas of the right SLF was significantly reduced (p <.05). Patients with VH also showed an altered functional connectivity in the ventral attention network, connected by the ventral portion of the SLF (p <.05). Conclusions: Our findings suggest that a combination of microstructural and functional alterations involving the attention networks in the right hemisphere may be important in the genesis of VH. © 2021 Elsevier Ltd

Author Keywords
Dementia with Lewy bodies;  DTI;  MRI;  Visual hallucination;  White matter

Funding details
Horizon 2020 Framework ProgrammeH202081852
European Research CouncilERC
Ministero dell’Istruzione, dell’Università e della RicercaMIUR
Horizon 2020
Associazione Italiana Ricerca Alzheimer

Immune activation during Paenibacillus brain infection in African infants with frequent cytomegalovirus co-infection
(2021) iScience, 24 (4), art. no. 102351, . 

Isaacs, A.M.^a b , Morton, S.U.^c d , Movassagh, M.^e , Zhang, Q.^f , Hehnly, C.^g h , Zhang, L.^g , Morales, D.M.ⁱ , Sinnar, S.A.^j k , Ericson, J.E.^l , Mbabazi-Kabachelor, E.^m , Ssenyonga, P.^m , Onen, J.^m , Mulondo, R.^m , Hornig, M.ⁿ , Warf, B.C.^o , Broach, J.R.^g h , Townsend, R.R.^f , Limbrick, D.D., Jr.ⁱ , Paulson, J.N.^p , Schiff, S.J.^j q

^a Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States
^b Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N 1N4, Canada
^c Division of Newborn Medicine, Boston Children’s Hospital, Boston, MA 02115, United States
^d Department of Pediatrics, Harvard Medical School, Boston, MA 02115, United States
^e Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, United States
^f Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
^g Institute for Personalized Medicine, Pennsylvania State University, Hershey, PA 17033, United States
^h Department of Biochemistry and Molecular Biology, Pennsylvania State University, State College, PA 16801, United States
ⁱ Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO 63110, United States
^j Center for Neural Engineering, Pennsylvania State University, State College, PA 16801, United States
^k Department of Medicine, Pennsylvania State University College of Medicine, Hershey, PA 17033, United States
^l Department of Pediatrics, Pennsylvania State College of Medicine, Hershey, PA 17033, United States
^m CURE Children’s Hospital of Uganda, Mbale, Uganda
ⁿ Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY 10032, United States
^o Department of Neurosurgery, Harvard Medical School, Boston, MA 02115, United States
^p Department of Biostatistics, Product Development, Genentech Inc., South San Francisco, CA 94080, United States
^q Center for Infectious Disease Dynamics, Departments of Neurosurgery, Engineering Science and Mechanics, and Physics, The Pennsylvania State University, University ParkPA 16802, United States

Abstract
Inflammation during neonatal brain infections leads to significant secondary sequelae such as hydrocephalus, which often follows neonatal sepsis in the developing world. In 100 African hydrocephalic infants we identified the biological pathways that account for this response. The dominant bacterial pathogen was a Paenibacillus species, with frequent cytomegalovirus co-infection. A proteogenomic strategy was employed to confirm host immune response to Paenibacillus and to define the interplay within the host immune response network. Immune activation emphasized neuroinflammation, oxidative stress reaction, and extracellular matrix organization. The innate immune system response included neutrophil activity, signaling via IL-4, IL-12, IL-13, interferon, and Jak/STAT pathways. Platelet-activating factors and factors involved with microbe recognition such as Class I MHC antigen-presenting complex were also increased. Evidence suggests that dysregulated neuroinflammation propagates inflammatory hydrocephalus, and these pathways are potential targets for adjunctive treatments to reduce the hazards of neuroinflammation and risk of hydrocephalus following neonatal sepsis. © 2021 The Authors

Author Keywords
Immunology;  Proteomics;  Transcriptomics

Funding details
396212
National Institutes of HealthNIH5DP1HD086071-05
National Cancer InstituteNCIP30 CA091842
National Institute of General Medical SciencesNIGMSP41 GM103422, R24GM136766
Medtronic
National Center for Advancing Translational SciencesNCATSUL1 TR000448
Institute of Clinical and Translational SciencesICTS
Pennsylvania State UniversityPSU

SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration
(2021) Neuron, 109 (7), pp. 1118-1136.e11. Cited 1 time.

Figley, M.D.^a b , Gu, W.^c , Nanson, J.D.^c , Shi, Y.^d , Sasaki, Y.^b e , Cunnea, K.^f g , Malde, A.K.^d , Jia, X.^h , Luo, Z.^c , Saikot, F.K.^c , Mosaiab, T.^d , Masic, V.^d , Holt, S.^d , Hartley-Tassell, L.^d , McGuinness, H.Y.^c , Manik, M.K.^c , Bosanac, T.ⁱ , Landsberg, M.J.^c , Kerry, P.S.^f g , Mobli, M.^h , Hughes, R.O.ⁱ , Milbrandt, J.^b e , Kobe, B.^c , DiAntonio, A.^a b , Ve, T.^d

^a Department of Developmental Biology, Washington University School of Medicine in Saint Louis, St. Louis, MO, United States
^b Needleman Center for Neurometabolism and Axonal Therapeutics, Washington University School of Medicine in Saint Louis, St. Louis, MO, United States
^c School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia
^d Institute for Glycomics, Griffith University, Southport, QLD 4222, Australia
^e Department of Genetics, Washington University School of Medicine in Saint Louis, St. Louis, MO, United States
^f Evotec (UK) Ltd., 114 Innovation Drive, Milton Park, Abingdon, Oxfordshire OX14 4RZ, United Kingdom
^g Evotec SE, Manfred Eigen Campus, Essener Bogen 7, Hamburg, 22419, Germany
^h Centre for Advanced Imaging, University of Queensland, Brisbane, QLD 4072, Australia
ⁱ Disarm Therapeutics, a wholly owned subsidiary of Eli Lilly & Co., Cambridge, MA, United States

Abstract
Axon degeneration is a central pathological feature of many neurodegenerative diseases. Sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM1) is a nicotinamide adenine dinucleotide (NAD+)-cleaving enzyme whose activation triggers axon destruction. Loss of the biosynthetic enzyme NMNAT2, which converts nicotinamide mononucleotide (NMN) to NAD+, activates SARM1 via an unknown mechanism. Using structural, biochemical, biophysical, and cellular assays, we demonstrate that SARM1 is activated by an increase in the ratio of NMN to NAD+ and show that both metabolites compete for binding to the auto-inhibitory N-terminal armadillo repeat (ARM) domain of SARM1. We report structures of the SARM1 ARM domain bound to NMN and of the homo-octameric SARM1 complex in the absence of ligands. We show that NMN influences the structure of SARM1 and demonstrate via mutagenesis that NMN binding is required for injury-induced SARM1 activation and axon destruction. Hence, SARM1 is a metabolic sensor responding to an increased NMN/NAD+ ratio by cleaving residual NAD+, thereby inducing feedforward metabolic catastrophe and axonal demise. © 2021 Elsevier Inc.

Author Keywords
allostery;  ARM domain;  cryo-EM;  NADase;  nicotinamide riboside;  TIR domain;  X-ray crystallography

CD11c+CD88+CD317+ myeloid cells are critical mediators of persistent CNS autoimmunity
(2021) Proceedings of the National Academy of Sciences of the United States of America, 118 (14), . 

Manouchehri, N.^a , Hussain, R.Z.^a , Cravens, P.D.^a , Esaulova, E.^b , Artyomov, M.N.^b , Edelson, B.T.^b , Wu, G.F.^b c , Cross, A.H.^c , Doelger, R.^a , Loof, N.^d , Eagar, T.N.^e , Forsthuber, T.G.^f , Calvier, L.^g h , Herz, J.^g h i j , Stüve, O.^k l

^a Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
^b Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110
^c Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110
^d Moody Foundation Flow Cytometry Facility, Children’s Research Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
^e Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030
^f Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, Mexico
^g Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
^h Center for Translational Neurodegeneration Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
ⁱ Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
^j Center for Neuroscience, Department of Neuroanatomy, Albert-Ludwigs University, Freiburg, 79085, Germany
^k Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390;
^l Neurology Section, VA North Texas Health Care System, Dallas, United States

Abstract
Natalizumab, a humanized monoclonal antibody (mAb) against α4-integrin, reduces the number of dendritic cells (DC) in cerebral perivascular spaces in multiple sclerosis (MS). Selective deletion of α4-integrin in CD11c+ cells should curtail their migration to the central nervous system (CNS) and ameliorate experimental autoimmune encephalomyelitis (EAE). We generated CD11c.Cre+/-ITGA4fl/fl C57BL/6 mice to selectively delete α4-integrin in CD11c+ cells. Active immunization and adoptive transfer EAE models were employed and compared with WT controls. Multiparameter flow cytometry was utilized to immunophenotype leukocyte subsets. Single-cell RNA sequencing was used to profile individual cells. α4-Integrin expression by CD11c+ cells was significantly reduced in primary and secondary lymphoid organs in CD11c.Cre+/-ITGA4fl/fl mice. In active EAE, a delayed disease onset was observed in CD11c.Cre+/-ITGA4fl/fl mice, during which CD11c+CD88+ cells were sequestered in the blood. Upon clinical EAE onset, CD11c+CD88+ cells appeared in the CNS and expressed CD317+ In adoptive transfer experiments, CD11c.Cre+/-ITGA4fl/fl mice had ameliorated clinical disease phenotype associated with significantly diminished numbers of CNS CD11c+CD88+CD317+ cells. In human cerebrospinal fluid from subjects with neuroinflammation, microglia-like cells display coincident expression of ITGAX (CD11c), C5AR1 (CD88), and BST2 (CD317). In mice, we show that only activated, but not naïve microglia expressed CD11c, CD88, and CD317. Finally, anti-CD317 treatment prior to clinical EAE substantially enhanced recovery in mice. Copyright © 2021 the Author(s). Published by PNAS.

Author Keywords
biomarker;  CD317;  EAE;  multiple sclerosis;  myeloid cells

Striatal dopamine mediates hallucination-like perception in mice
(2021) Science, 372 (6537), art. no. 51, . 

Schmack, K.^a , Bosc, M.^a , Ott, T.^b , Sturgill, J.F.^a , Kepecs, A.^a b

^a Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, United States
^b Departments of Neuroscience and Psychiatry, Washington University, School of Medicine, St. Louis, MO 63110, United States

Abstract
Hallucinations, a central symptom of psychotic disorders, are attributed to excessive dopamine in the brain. However, the neural circuit mechanisms by which dopamine produces hallucinations remain elusive, largely because hallucinations have been challenging to study in model organisms. We developed a task to quantify hallucination-like perception in mice. Hallucination-like percepts, defined as high-confidence false detections, increased after hallucination-related manipulations in mice and correlated with self-reported hallucinations in humans. Hallucination-like percepts were preceded by elevated striatal dopamine levels, could be induced by optogenetic stimulation of mesostriatal dopamine neurons, and could be reversed by the antipsychotic drug haloperidol. These findings reveal a causal role for dopamine-dependent striatal circuits in hallucination-like perception and open new avenues to develop circuit-based treatments for psychotic disorders. © 2021 American Association for the Advancement of Science. All rights reserved.

Management of sagittal synostosis in the Synostosis Research Group: baseline data and early outcomes
(2021) Neurosurgical Focus, 50 (4), pp. 1-6. 

Baker, C.M.^a , Ravindra, V.M.^a b c , Gociman, B.^d , Siddiqi, F.A.^d , Goldstein, J.A.^e , Smyth, M.D.^f , Lee, A.^g , Anderson, R.C.E.^h , Patel, K.B.ⁱ , Birgfeld, C.^j , Pollack, I.F.^j , Imahiyerobo, T.^k , Kestle, J.R.W.^a

^a Divisions of Pediatric Neurosurgery, Primary Children’s Hospital, Salt Lake City, Utah, United States
^b Division of Neurosurgery, University of California, San Diego, California, United States
^c Department of Neurosurgery, Naval Medical Center San DiegoCalifornia
^d Divisions of Plastic and Reconstructive Surgery, University of Utah, Salt Lake City, Utah, United States
^e Departments of Plastic SurgeryPennsylvania, United States
^f Department of NeurosurgeryMissouri, United States
^g Department of Neurosurgery, Seattle Children’s Hospital, University of Washington, Seattle, Washington, United States
^h Department of Neurosurgery, Columbia University, Morgan Stanley Children’s Hospital, New York, United States
ⁱ Division of Plastic and Reconstructive Surgery, Department of Surgery, St. Louis Children’s Hospital, Washington University School of Medicine in St. LouisMissouri, United States
^j Departments of Pediatric Neurosurgery, UPMC Children’s Hospital of PittsburghPennsylvania, United States
^k Division of Plastic Surgery, Columbia University Medical Center, NewYork-Presbyterian Hospital, New York, New York, United States

Abstract
Objective Sagittal synostosis is the most common form of isolated craniosynostosis. Although some centers have reported extensive experience with this condition, most reports have focused on a single center. In 2017, the Synostosis Research Group (SynRG), a multicenter collaborative network, was formed to study craniosynostosis. Here, the authors report their early experience with treating sagittal synostosis in the network. The goals were to describe practice patterns, identify variations, and generate hypotheses for future research. Methods All patients with a clinical diagnosis of isolated sagittal synostosis who presented to a SynRG center between March 1, 2017, and October 31, 2019, were included. Follow-up information through October 31, 2020, was included. Data extracted from the prospectively maintained SynRG registry included baseline parameters, surgical adjuncts and techniques, complications prior to discharge, and indications for reoperation. Data analysis was descriptive, using frequencies for categorical variables and means and medians for continuous variables. Results Two hundred five patients had treatment for sagittal synostosis at 5 different sites. One hundred twenty-six patients were treated with strip craniectomy and 79 patients with total cranial vault remodeling. The most common strip craniectomy was wide craniectomy with parietal wedge osteotomies (44%), and the most common cranial vault remodeling procedure was total vault remodeling without forehead remodeling (63%). Preoperative mean cephalic indices (CIs) were similar between treatment groups: 0.69 for strip craniectomy and 0.68 for cranial vault remodeling. Thirteen percent of patients had other health problems. In the cranial vault cohort, 81% of patients who received tranexamic acid required a transfusion compared with 94% of patients who did not receive tranexamic acid. The rates of complication were low in all treatment groups. Five patients (2%) had an unintended reoperation. The mean change in CI was 0.09 for strip craniectomy and 0.06 for cranial vault remodeling; wide craniectomy resulted in a greater change in CI in the strip craniectomy group. Conclusions The baseline severity of scaphocephaly was similar across procedures and sites. Treatment methods varied, but cranial vault remodeling and strip craniectomy both resulted in satisfactory postoperative CIs. Use of tranexamic acid may reduce the need for transfusion in cranial vault cases. The wide craniectomy technique for strip craniectomy seemed to be associated with change in CI. Both findings seem amenable to testing in a randomized controlled trial. ©AANS 2021, except where prohibited by US copyright law

Author Keywords
cranial vault reconstruction;  craniosynostosis;  sagittal synostosis;  strip craniectomy;  Synostosis Research Group

Funding details
University of Utah

Hydrocephalus treatment in patients with craniosynostosis: an analysis from the Hydrocephalus Clinical Research Network prospective registry
(2021) Neurosurgical Focus, 50 (4), pp. 1-7. 

Bonfield, C.M.^a , Shannon, C.N.^a , Reeder, R.W.^b , Browd, S.^c , Drake, J.^d , Hauptman, J.S.^c , Kulkarni, A.V.^d , Limbrick, D.D.^e , McDonald, P.J.^f , Naftel, R.^a , Pollack, I.F.^g , Riva-Cambrin, J.^h , Rozzelle, C.ⁱ , Tamber, M.S.^f , Whitehead, W.E.^j , Kestle, J.R.W.^k , III, J.C.W.^a

^a Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States
^b Departments of Pediatrics, Salt Lake City, Utah, United States
^c Department of Neurosurgery, University of Washington, Seattle, Washington, United States
^d Division of Neurosurgery, University of Toronto, Ontario, Canada
^e Department of Neurosurgery, Washington University School of Medicine in St. LouisMissouri, United States
^f Division of Neurosurgery, University of British Columbia, British Columbia, Vancouver, Canada
^g Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
^h Division of Neurosurgery, University of Calgary, Alberta, Canada
ⁱ Department of Neurosurgery, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States
^j Department of Neurosurgery, Baylor College of Medicine, Houston, Texas
^k Department of Neurosurgery, University of Utah, Salt Lake City, Utah, United States

Abstract
Objective Hydrocephalus may be seen in patients with multisuture craniosynostosis and, less commonly, singlesuture craniosynostosis. The optimal treatment for hydrocephalus in this population is unknown. In this study, the authors aimed to evaluate the success rate of ventriculoperitoneal shunt (VPS) treatment and endoscopic third ventriculostomy (ETV) both with and without choroid plexus cauterization (CPC) in patients with craniosynostosis. Methods Utilizing the Hydrocephalus Clinical Research Network (HCRN) Core Data Project (Registry), the authors identified all patients who underwent treatment for hydrocephalus associated with craniosynostosis. Descriptive statistics, demographics, and surgical outcomes were evaluated. Results In total, 42 patients underwent treatment for hydrocephalus associated with craniosynostosis. The median gestational age at birth was 39.0 weeks (IQR 38.0, 40.0); 55% were female and 60% were White. The median age at first craniosynostosis surgery was 0.6 years (IQR 0.3, 1.7), and at the first permanent hydrocephalus surgery it was 1.2 years (IQR 0.5, 2.5). Thirty-three patients (79%) had multiple different sutures fused, and 9 had a single suture: 3 unicoronal (7%), 3 sagittal (7%), 2 lambdoidal (5%), and 1 unknown (2%). Syndromes were identified in 38 patients (90%), with Crouzon syndrome being the most common (n = 16, 42%). Ten patients (28%) received permanent hydrocephalus surgery before the first craniosynostosis surgery. Twenty-eight patients (67%) underwent VPS treatment, with the remaining 14 (33%) undergoing ETV with or without CPC (ETV ± CPC). Within 12 months after initial hydrocephalus intervention, 14 patients (34%) required revision (8 VPS and 6 ETV ± CPC). At the most recent follow-up, 21 patients (50%) required a revision. The revision rate decreased as age increased. The overall infection rate was 5% (VPS 7%, 0% ETV ± CPC). Conclusions This is the largest prospective study reported on children with craniosynostosis and hydrocephalus. Hydrocephalus in children with craniosynostosis most commonly occurs in syndromic patients and multisuture fusion. It is treated at varying ages; however, most patients undergo surgery for craniosynostosis prior to hydrocephalus treatment. While VPS treatment is performed more frequently, VPS and ETV are both reasonable options, with decreasing revision rates with increasing age, for the treatment of hydrocephalus associated with craniosynostosis. ©AANS 2021, except where prohibited by US copyright law

Author Keywords
craniosynostosis;  endoscopic third ventriculostomy;  hydrocephalus;  ventriculoperitoneal shunt

Funding details
National Institute of Neurological Disorders and StrokeNINDS1RC1NS068943-01, CER-1403-13857
Gerber Foundation1692-3638
Hydrocephalus AssociationHA

Left Ventricular Dysfunction and Depression in Hospitalized Patients with Heart Failure
(2021) Psychosomatic Medicine, 83 (3), pp. 274-282. 

Freedland, K.E., Carney, R.M., Steinmeyer, B.C., Skala, J.A., Rich, M.W.

From the Washington University School of Medicine, St. Louis, MO, United States

Abstract
OBJECTIVE: This study examined whether the severity of left ventricular systolic dysfunction is associated with depression in patients with heart failure (HF). Other factors were also studied to identify independent correlates of depression in HF. METHODS: The sample consisted of 400 hospitalized patients with HF. Left ventricular ejection fraction and other medical data were obtained from medical records. Depression and other psychosocial characteristics were assessed by an interview and questionnaires. Proportional odds models were used to test the relationships of these characteristics to Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) depressive disorders, and analysis of covariance was used to test relationships with continuous measures of depression in secondary models. RESULTS: The models produced no evidence of an association between left ventricular ejection fraction and depression. The adjusted odds ratio (95% confidence interval) was 1.00 (0.98-1.01; p = .87) for depression diagnosis. Analysis of covariance estimates (standard errors) were -0.01 (0.02; p = .54) for the Hamilton Rating Scale for Depression and -0.01 (0.01; p = .59) for the Patient Health Questionnaire. The odds of depression were higher in African American patients and in those with high levels of anxiety or stress. Other characteristics that have been associated with depression in previous studies, including sex and age, were not consistently associated with depression in this study. CONCLUSIONS: There is no relationship between the severity of left ventricular systolic dysfunction and depression in hospitalized patients with HF. In contrast, African American patients and those with a high level of anxiety or perceived stress are more likely than other patients to have a comorbid depressive disorder. Copyright © 2021 by the American Psychosomatic Society.

Dural augmentation approaches and complication rates after posterior fossa decompression for Chiari I malformation and syringomyelia: A Park-Reeves Syringomyelia Research Consortium study
(2021) Journal of Neurosurgery: Pediatrics, 27 (4), pp. 459-468. 

Yahanda, A.T.^a , David Adelson, P.^b , Hassan A. Akbari, S.^c , Albert, G.W.^d , Aldana, P.R.^e , Alden, T.D.^f , Anderson, R.C.E.^g , Bauer, D.F.^h , Bethel-Anderson, T.^a , Brockmeyer, D.L.ⁱ , Chern, J.J.^j , Couture, D.E.^k , Daniels, D.J.^l , Dlouhy, B.J.^m , Durham, S.R.ⁿ , Ellenbogen, R.G.^o , Eskandari, R.^p , George, T.M.^q , Grant, G.A.^r , Graupman, P.C.^s , Greene, S.^t , Greenfield, J.P.^u , Gross, N.L.^v , Guillaume, D.J.^w , Hankinson, T.C.^x , Heuer, G.G.^y , Iantosca, M.^z , Iskandar, B.J.^aa , Jackson, E.M.^ab , Johnston, J.M.^c , Keating, R.F.^ac , Krieger, M.D.^ad , Leonard, J.R.^ae , Maher, C.O.^af , Mangano, F.T.^ag , Gordon McComb, J.^ad , McEvoy, S.D.^a , Meehan, T.^a , Menezes, A.H.^m , O’Neill, B.R.^x , Olavarria, G.^ah , Ragheb, J.^ai , Selden, N.R.^aj , Shah, M.N.^ak , Shannon, C.N.^al , Shimony, J.S.^am , Smyth, M.D.^a , Stone, S.S.D.^an , Strahle, J.M.^a , Torner, J.C.^m , Tuite, G.F.^ao , Wait, S.D.^ap , Wellons, J.C., III^al , Whitehead, W.E.^aq , Park, T.S.^a , Limbrick, D.D., Jr.^a

^a Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States
^b Division of Pediatric Neurosurgery, Barrow Neurological Institute at Phoenix Children’s Hospital, Phoenix, AZ, United States
^c Division of Pediatric Neurosurgery, University of Alabama at BirminghamAL, United States
^d Division of Neurosurgery, Arkansas Children’s Hospital, Little Rock, AR, United States
^e Division of Pediatric Neurosurgery, University of Florida College of Medicine, Jacksonville, FL, United States
^f Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children’s Hospital of ChicagoIL, United States
^g Division of Pediatric Neurosurgery, Department of Neurological Surgery, Children’s Hospital of New York, Columbia-Presbyterian, New York, NY, United States
^h Department of Neurosurgery, Dartmouth- Hitchcock Medical Center, Lebanon, NH, United States
ⁱ Division of Pediatric Neurosurgery, Primary Children’s Hospital, Salt Lake City, UT, United States
^j Division of Pediatric Neurosurgery, Children’s Healthcare of AtlantaGA, United States
^k Department of Neurological Surgery, Wake Forest University, School of Medicine, Winston-Salem, NC, United States
^l Department of Neurosurgery, Mayo Clinic, Rochester, MN, United States
^m Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, IA, United States
ⁿ Department of Neurosurgery, University of Vermont, Burlington, VT, United States
^o Division of Pediatric Neurosurgery, Seattle Children’s Hospital, Seattle, WA, United States
^p Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, United States
^q Division of Pediatric Neurosurgery, Dell Children’s Medical Center, Austin, TX, United States
^r Division of Pediatric Neurosurgery, Lucile Packard Children’s Hospital, Palo Alto, CA, United States
^s Division of Pediatric Neurosurgery, Gillette Children’s Hospital, St. Paul, MN, United States
^t Division of Pediatric Neurosurgery, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
^u Department of Neurological Surgery, Weill Cornell Medical College, NewYork-Presbyterian Hospital, New York, NY, United States
^v Department of Neurosurgery, University of Oklahoma, Oklahoma City, OK, United States
^w Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN, United States
^x Department of Neurosurgery, Children’s Hospital Colorado, Aurora, CO, United States
^y Division of Pediatric Neurosurgery, Children’s Hospital of Pennsylvania, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
^z Department of Neurosurgery, Penn State Milton S. Hershey Medical Center, Hershey, PA, United States
^aa Department of Neurological Surgery, University of Wisconsin at MadisonWI, United States
^ab Department of Neurosurgery, Johns Hopkins University, School of Medicine, Baltimore, MD, United States
^ac Department of Neurosurgery, Children’s National Medical Center, Washington, DC, United States
^ad Division of Pediatric Neurosurgery, Children’s Hospital of Los AngelesCA, United States
^ae Division of Pediatric Neurosurgery, Nationwide Children’s Hospital, Columbus, OH, United States
^af Department of Neurosurgery, University of Michigan, Ann Arbor, MI, United States
^ag Division of Pediatric Neurosurgery, Cincinnati Children’s Medical Center, Cincinnati, OH, United States
^ah Division of Pediatric Neurosurgery, Arnold Palmer Hospital for Children, Orlando, FL, United States
^ai Department of Neurological Surgery, University of Miami, School of Medicine, Miami, FL, United States
^aj Department of Neurological Surgery and Doernbecher Children’s Hospital, Oregon Health and Science University, Portland, OR, United States
^ak Division of Pediatric Neurosurgery, McGovern Medical School, Houston, TX, United States
^al Division of Pediatric Neurosurgery, Monroe Carell Jr. Children’s Hospital of Vanderbilt University, Nashville, TN, United States
^am Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
^an Division of Pediatric Neurosurgery, Boston Children’s Hospital, Boston, MA, United States
^ao Department of Neurosurgery, Neuroscience Institute, All Children’s Hospital, St. Petersburg, FL, United States
^ap Carolina Neurosurgery and Spine Associates, Charlotte, NC, United States
^aq Division of Pediatric Neurosurgery, Texas Children’s Hospital, Houston, TX, United States

Abstract
OBJECTIVE Posterior fossa decompression with duraplasty (PFDD) is commonly performed for Chiari I malformation (CM-I) with syringomyelia (SM). However, complication rates associated with various dural graft types are not well established. The objective of this study was to elucidate complication rates within 6 months of surgery among autograft and commonly used nonautologous grafts for pediatric patients who underwent PFDD for CM-I/SM. METHODS The Park-Reeves Syringomyelia Research Consortium database was queried for pediatric patients who had undergone PFDD for CM-I with SM. All patients had tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and ≥ 6 months of postoperative follow-up after PFDD. Complications (e.g., pseudomeningocele, CSF leak, meningitis, and hydrocephalus) and postoperative changes in syrinx size, headaches, and neck pain were compared for autograft versus nonautologous graft. RESULTS A total of 781 PFDD cases were analyzed (359 autograft, 422 nonautologous graft). Nonautologous grafts included bovine pericardium (n = 63), bovine collagen (n = 225), synthetic (n = 99), and human cadaveric allograft (n = 35). Autograft (103/359, 28.7%) had a similar overall complication rate compared to nonautologous graft (143/422, 33.9%) (p = 0.12). However, nonautologous graft was associated with significantly higher rates of pseudomeningocele (p = 0.04) and meningitis (p < 0.001). The higher rate of meningitis was influenced particularly by the higher rate of chemical meningitis (p = 0.002) versus infectious meningitis (p = 0.132). Among 4 types of nonautologous grafts, there were differences in complication rates (p = 0.02), including chemical meningitis (p = 0.01) and postoperative nausea/ vomiting (p = 0.03). Allograft demonstrated the lowest complication rates overall (14.3%) and yielded significantly fewer complications compared to bovine collagen (p = 0.02) and synthetic (p = 0.003) grafts. Synthetic graft yielded higher complication rates than autograft (p = 0.01). Autograft and nonautologous graft resulted in equal improvements in syrinx size (p < 0.0001). No differences were found for postoperative changes in headaches or neck pain. CONCLUSIONS In the largest multicenter cohort to date, complication rates for dural autograft and nonautologous graft are similar after PFDD for CM-I/SM, although nonautologous graft results in higher rates of pseudomeningocele and meningitis. Rates of meningitis differ among nonautologous graft types. Autograft and nonautologous graft are equivalent for reducing syrinx size, headaches, and neck pain. © 2021 American Association of Neurological Surgeons. All rights reserved.

Author Keywords
Chiari I malformation;  Dural augmentation;  Duraplasty;  Park-Reeves;  Posterior fossa decompression;  Syringomyelia

Funding details
National Institutes of HealthNIHU54 HD087011
University of WashingtonUW
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD

Dysfunction of the proteoglycan Tsukushi causes hydrocephalus through altered neurogenesis in the subventricular zone in mice
(2021) Science Translational Medicine, 13 (587), art. no. e7896, . 

Ito, N.^a b , Riyadh, M.A.^a b c , Ahmad, S.A.I.^a b d , Hattori, S.^e , Kanemura, Y.^f , Kiyonari, H.^g , Abe, T.^g , Furuta, Y.^g h , Shinmyo, Y.^a b i , Kaneko, N.^j , Hirota, Y.^j k , Lupo, G.^l , Hatakeyama, J.^m , Felemban Athary Abdulhaleem, M.^a b n , Anam, M.B.^a b o , Yamaguchi, M.^p , Takeo, T.^q , Takebayashi, H.^r , Takebayashi, M.^s , Oike, Y.^t , Nakagata, N.^q , Shimamura, K.^m , Holtzman, M.J.^u , Takahashi, Y.^v w , Guillemot, F.^x , Miyakawa, T.^e , Sawamoto, K.^j y , Ohta, K.^{a b o w z}

^a Department of Developmental Neurobiology, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
^b Stem Cell-Based Tissue Regeneration Research and Education Unit, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
^c Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia
^d Department of Biotechnology and Genetic Engineering, Mawlana Bhashani Science and Technology University, Tangail, 1902, Bangladesh
^e Division of System Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, 470-1192, Japan
^f Department of Biomedical Research and Innovation, Institute for Clinical Research, National Hospital Organization Osaka National Hospital, 2-1-14, Hoensaka, Chuo-ku, Osaka, 540-0006, Japan
^g Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima Minami-machi, Chuou-ku, Kobe, 650-0047, Japan
^h Mouse Genetics Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10021, United States
ⁱ Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, 13-1, Takara-cho, Ishikawa, 920-8640, Japan
^j Depart-ment of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University, Graduate School of Medical Sciences, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan
^k Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
^l Department of Biology and Biotechnology “C. Darwin”, Sapienza University of Rome, Piazzale Aldo Moro 5, Rome, 00185, Italy
^m Department of Brain Morphogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan
ⁿ Department of Biology, Faculty of Applied Science, Umm Al-Qura University, Makkah, 21955, Saudi Arabia
^o Program for Leading Graduate Schools “HIGO Program”, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
^p Department of Physiology, Kochi Medical School, Kochi University, Kochi, 783-8505, Japan
^q Division of Reproductive Engineering, Center for Animal Resources and Development (CARD), Kumamoto University, 2-2-1 Honjo, Kumamoto, 860-0811, Japan
^r Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi, Chuo-ku, Niigata 951-8510, Japan
^s Department of Neuropsychiatry, Faculty of Life Science, Kumamoto University, Kumamoto, 860-8556, Japan
^t Department of Molecular Genetics, Graduate School of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
^u Pulmonary and Critical Care Medicine, Department of Medicine, Washington University, School of Medicine, St. Louis, MO 63110-1093, United States
^v Department of Zoology, Graduate School of Science, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto, 606-8502, Japan
^w AMED Core Research for Evolutional Science and Technology (AMED-CREST), Japan Agency for Medical Research and Development (AMED), Chiyoda-ku, Tokyo, 100-0004, Japan
^x The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, United Kingdom
^y Divi-sion of Neural Development and Regeneration, National Institute for Physiological Sciences, Okazaki, 444-8585, Japan
^z Department of Stem Cell Biology, Faculty of Arts and Science, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan

Abstract
The lateral ventricle (LV) is flanked by the subventricular zone (SVZ), a neural stem cell (NSC) niche rich in extrinsic growth factors regulating NSC maintenance, proliferation, and neuronal differentiation. Dysregulation of the SVZ niche causes LV expansion, a condition known as hydrocephalus; however, the underlying pathological mechanisms are unclear. We show that deficiency of the proteoglycan Tsukushi (TSK) in ependymal cells at the LV surface and in the cerebrospinal fluid results in hydrocephalus with neurodevelopmental disorder-like symptoms in mice. These symptoms are accompanied by altered differentiation and survival of the NSC lineage, disrupted ependymal structure, and dysregulated Wnt signaling. Multiple TSK variants found in patients with hydrocephalus exhibit reduced physiological activity in mice in vivo and in vitro. Administration of wild-type TSK protein or Wnt antagonists, but not of hydrocephalus-related TSK variants, in the LV of TSK knockout mice prevented hydrocephalus and preserved SVZ neurogenesis. These observations suggest that TSK plays a crucial role as a niche molecule modulating the fate of SVZ NSCs and point to TSK as a candidate for the diagnosis and therapy of hydrocephalus. Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

Defining Surgical Terminology and Risk for Brain Computer Interface Technologies
(2021) Frontiers in Neuroscience, 15, art. no. 599549, . 

Leuthardt, E.C.^{a b c d e f g} , Moran, D.W.^a b , Mullen, T.R.^h

^a Department of Biomedical Engineering, Washington University, St. Louis, MO, United States
^b Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States
^c Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
^d Department of Mechanical Engineering and Materials Science, Washington University, St. Louis, MO, United States
^e Center for Innovation in Neuroscience and Technology, Washington University School of Medicine, St. Louis, MO, United States
^f Brain Laser Center, Washington University School of Medicine, St. Louis, MO, United States
^g Division of Neurotechnology, Washington University School of Medicine, St. Louis, MO, United States
^h Intheon Labs, San Diego, CA, United States

Abstract
With the emergence of numerous brain computer interfaces (BCI), their form factors, and clinical applications the terminology to describe their clinical deployment and the associated risk has been vague. The terms “minimally invasive” or “non-invasive” have been commonly used, but the risk can vary widely based on the form factor and anatomic location. Thus, taken together, there needs to be a terminology that best accommodates the surgical footprint of a BCI and their attendant risks. This work presents a semantic framework that describes the BCI from a procedural standpoint and its attendant clinical risk profile. We propose extending the common invasive/non-invasive distinction for BCI systems to accommodate three categories in which the BCI anatomically interfaces with the patient and whether or not a surgical procedure is required for deployment: (1) Non-invasive—BCI components do not penetrate the body, (2) Embedded—components are penetrative, but not deeper than the inner table of the skull, and (3) Intracranial –components are located within the inner table of the skull and possibly within the brain volume. Each class has a separate risk profile that should be considered when being applied to a given clinical population. Optimally, balancing this risk profile with clinical need provides the most ethical deployment of these emerging classes of devices. As BCIs gain larger adoption, and terminology becomes standardized, having an improved, more precise language will better serve clinicians, patients, and consumers in discussing these technologies, particularly within the context of surgical procedures. © Copyright © 2021 Leuthardt, Moran and Mullen.

Author Keywords
brain computer interface (BCI);  ECOG;  EEG;  local field potential;  neuroprosthetic;  single neuron;  surgical risk;  terminology

IgG4-Related Disease of the Skull and Skull Base–A Systematic Review and Report of Two Cases
(2021) World Neurosurgery, . 

Cler, S.J.^a , Sharifai, N.^b , Baker, B.^c , Dowling, J.L.^a , Pipkorn, P.^d , Yaeger, L.^f , Clifford, D.B.^c e , Dahiya, S.^b , Chicoine, M.R.^a

^a Department of Neurosurgery, Washington University School of Medicine, Washington, DC, United States
^b Department of Pathology and Immunology, Washington University School of Medicine, Washington, DC, United States
^c Department of Neurology, Washington University School of Medicine, Washington, DC, United States
^d Department of Otolaryngology, Washington University School of Medicine, Washington, DC, United States
^e Department of Infectious Disease, Washington University School of Medicine, Washington, DC, United States
^f Bernard Becker Medical Library, Washington University School of Medicine, Washington, DC, United States

Abstract
Objective: IgG4-related disease (IgG4-RD) is an inflammatory process that uncommonly can present in the skull base and calvarium and mimic a tumor but the nature of this condition is not well summarized in the neurosurgical literature. Methods: A review was performed of 2 cases of IgG4-RD in the skull base highlighting the diagnostic challenges with assessment of these skull base lesions, and a systematic review of relevant literature was carried out. Results: A systematic review of the literature conducted in accordance with PRISMA guidelines identified 113 articles, with 184 cases of IgG4-RD in the skull base or calvarium. The most commonly affected locations include the meninges, cavernous sinus, base of the posterior fossa, clivus, and mastoid bone. Headache, visual and auditory disturbances, cranial nerve dysfunction, and seizures were the most common presenting symptoms. Medical treatment was highly successful and most commonly consisted of corticosteroids coadministered with immunosuppressive agents such as rituximab. Prevalence seemed to be equal between sexes, and serum IgG4 levels were increased in 61% of patients. Delayed diagnosis and a need for multiple biopsies were reported in numerous cases. Two cases of skull base IgG4-RD from the authors’ institution show the variable presentations of this disease. More invasive surgical biopsies were required in both cases, and corticosteroid treatment led to significant clinical improvement. Conclusions: IgG4-RD is an uncommon condition with an increasing body of reported cases that can affect the skull base and calvarium and should be in the differential diagnosis, because delay in diagnosis and treatment may be common. © 2021

Author Keywords
Calvarium;  IgG4-related disease;  Skull base

Funding details
UL1 TR000448
National Institutes of HealthNIH
National Institute of Mental HealthNIMH
National Institute on AgingNIA
National Heart, Lung, and Blood InstituteNHLBI
National Cancer InstituteNCIP30 CA091842
National Institute of Allergy and Infectious DiseasesNIAID
National Institute of Neurological Disorders and StrokeNINDS
National Center for Advancing Translational SciencesNCATS
Alvin J. Siteman Cancer Center
Mitsubishi Tanabe Pharma CorporationMTPC

Towards a Data-Driven Approach to Screen for Autism Risk at 12 Months of Age
(2021) Journal of the American Academy of Child and Adolescent Psychiatry, . 

Meera, S.S.^a b , Donovan, K.^a , Wolff, J.J.^c , Zwaigenbaum, L.^d , Elison, J.T.^c , Kinh, T.^a , Shen, M.D.^a , Estes, A.M.^e , Hazlett, H.C.^a , Watson, L.R.^a , Baranek, G.T.^f , Swanson, M.R.^g , St. John, T.^e , Burrows, C.A.^c , Schultz, R.T.^h , Dager, S.R.^e , Botteron, K.N.ⁱ , Pandey, J.^h , Piven, J.^a , IBIS Network^j

^a Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill
^b The National Institute of Mental Health and Neurosciences, Bangalore, India
^c University of Minnesota, Minneapolis, United States
^d University of Alberta, Edmonton, Canada; and the Autism Research Centre, Glenrose Rehabilitation Hospital, Edmonton, Canada
^e University of Washington, Seattle, United States
^f University of Southern California, Los Angeles
^g University of Texas at Dallas, Richardson, United States
^h Children’s Hospital of Philadelphia, University of Pennsylvania
ⁱ Washington University in St. LouisMO, United States

Abstract
Objective: This study aimed to develop a classifier for infants at 12 months of age based on a parent-report measure (the First Year Inventory v.2.0 [FYI]), for the following reasons: (1) to classify infants at elevated risk, above and beyond that attributable to familial risk status for ASD; and (2) to serve as a starting point to refine an approach for risk estimation in population samples. Method: A total of 54 high−familial risk (HR) infants later diagnosed with ASD (HR-ASD), 183 HR infants not diagnosed with ASD at 24 months of age (HR-Neg), and 72 low-risk controls participated in the study. All infants contributed FYI data at 12 months of age and had a diagnostic assessment for ASD at age 24 months. A data-driven, cross-validated analytic approach was used to develop a classifier to determine screening accuracy (eg, sensitivity) of the FYI to classify HR-ASD and HR-Neg. Results: The newly developed FYI classifier had an estimated sensitivity of 0.71 (95% CI: 0.50, 0.91) and specificity of 0.72 (95% CI: 0.49, 0.91). Conclusion: This classifier demonstrates the potential to improve current screening for ASD risk at 12 months of age in infants already at elevated familial risk for ASD, increasing opportunities for detection of autism risk in infancy. Findings from this study highlight the utility of combining parent-report measures with machine learning approaches. © 2020 American Academy of Child and Adolescent Psychiatry

Author Keywords
autism spectrum disorder;  first year;  high-risk;  parent report;  screening

Funding details
USIEF-2264/FNDPR/2017
National Institutes of HealthNIHR01-HD055741, U54HD079124
National Institute of Mental HealthNIMH
National Institute of Neurological Disorders and StrokeNINDS
National Institute of Environmental Health SciencesNIEHS
Simons FoundationSF
University of North CarolinaUNC
University of MinnesotaUMN
University of Utah
University of WashingtonUW
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD
Simons Foundation Autism Research InitiativeSFARI140209
University of AlbertaUofA