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Article ; Online: Neurological outcome following delayed traction and fixation in severe tetraparesis consecutive to posterior decompression for Chiari malformation: a case report.

Vigneul, Eric / Del Gaudio, Nicole / de Nijs, Loïc / Raftopoulos, Christian

Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery

2024

Abstract: Background: Chiari malformation type 1 (CM1) is a congenital hindbrain malformation characterized by herniation of the cerebellar tonsils below the foramen magnum. The term Chiari type 1.5 is used when herniation of the brainstem under the McRae line ... ...

Abstract	Background: Chiari malformation type 1 (CM1) is a congenital hindbrain malformation characterized by herniation of the cerebellar tonsils below the foramen magnum. The term Chiari type 1.5 is used when herniation of the brainstem under the McRae line and anomalies of the craniovertebral junction are also present. These conditions are associated with several symptoms and signs, including headache, neck pain, and spinal cord syndrome. For symptomatic patients, surgical decompression is recommended. When radiographic indicators of craniovertebral junction (CVJ) instability or symptoms related to ventral brainstem compression are present, CVJ fixation should also be considered. Case description: We report the case of a 13-year-old girl who presented with severe tetraparesis after posterior decompression for Chiari malformation type 1.5, followed 5 days later by partial C2 laminectomy. Several months after the initial surgery, she underwent two fixations, first without and then with intraoperative cervical traction, leading to significant neurological improvement. Discussion and conclusion: This case report underscores the importance of meticulous radiological analysis before CM surgery. For CM 1.5 patients with basilar invagination, CVJ fixation is recommended, and C2 laminectomy should be avoided. In the event of significant clinical deterioration due to nonadherence to these guidelines, our findings highlight the importance of traction with increased extension before fixation, even years after initial destabilizing surgery.
Language	English
Publishing date	2024-02-19
Publishing country	Germany
Document type	Journal Article
ZDB-ID	605988-0
ISSN	1433-0350 ; 0302-2803 ; 0256-7040
ISSN (online)	1433-0350
ISSN	0302-2803 ; 0256-7040
DOI	10.1007/s00381-024-06327-6
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Article: Modified Vertical Parasagittal Sub-Insular Hemispherotomy-Case Series and Technical Note.

Del Gaudio, Nicole / Ferrao Santos, Susana / Raftopoulos, Christian

Brain sciences

2023 Volume 13, Issue 10

Abstract: 1) Background: Hemispherotomy is the generally accepted treatment for hemispheric drug-resistant epilepsy (DRE). Lateral or vertical approaches are performed according to the surgeon's preference. Multiple technical variations have been proposed since ... ...

Abstract	(1) Background: Hemispherotomy is the generally accepted treatment for hemispheric drug-resistant epilepsy (DRE). Lateral or vertical approaches are performed according to the surgeon's preference. Multiple technical variations have been proposed since Delalande first described his vertical technique. We propose a sub-insular variation of the vertical parasagittal hemispherotomy (VPH) and describe our case series of patients operated on using this procedure. (2) Methods: Data from a continuous series of patients with hemispheric DRE who were operated on by the senior author (CR) using the modified sub-insular VPH technique were analyzed retrospectively. Pre-operative demographic and epilepsy characteristics, functional outcome, and surgical complications were extracted from medical charts. (3) Results: Twenty-five patients were operated on between August 2008 and August 2023; 23 have at least 3 months of follow-up. Of this group, 20 (86.9%) patients are seizure-free. Only two patients developed postoperative hydrocephalus (8.7%). All patients who were able to walk autonomously preoperatively and 20 (86.9%) of those with follow-up were able to walk without assistance. A total of 17 (74%) patients were able to perform adapted social activities at the latest follow-up. (4) Conclusions: Modified sub-insular VPH is a successful surgical technique for hemispheric DRE with seizure freedom rates similar to the largest series reported in the literature. Compared to other series, patients who were operated on with our modified technique had a lower rate of postoperative hydrocephalus and excellent long-term motor and cognitive outcomes.
Language	English
Publishing date	2023-09-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci13101395
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Article: A mouse model to study glutathione limitation

Timson, Rebecca C / Khan, Artem / Uygur, Beste / Saad, Marwa / Yeh, Hsi-Wen / DelGaudio, Nicole / Weber, Ross / Alwaseem, Hanan / Gao, Jing / Yang, Chingwen / Birsoy, Kıvanç

bioRxiv : the preprint server for biology

2024

Abstract: Glutathione (GSH) is a highly abundant tripeptide thiol that performs diverse protective and biosynthetic functions in cells. While changes in GSH availability are linked to many diseases, including cancer and neurodegenerative disorders, determining the ...

Abstract	Glutathione (GSH) is a highly abundant tripeptide thiol that performs diverse protective and biosynthetic functions in cells. While changes in GSH availability are linked to many diseases, including cancer and neurodegenerative disorders, determining the function of GSH in physiology and disease has been challenging due to its tight regulation. To address this, we generated cell and mouse models that express a bifunctional glutathione-synthesizing enzyme from
Language	English
Publishing date	2024-01-09
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.08.574722
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Article ; Online: Development of a mouse model expressing a bifunctional glutathione-synthesizing enzyme to study glutathione limitation in vivo.

Timson, Rebecca C / Khan, Artem / Uygur, Beste / Saad, Marwa / Yeh, Hsi-Wen / DelGaudio, Nicole L / Weber, Ross / Alwaseem, Hanan / Gao, Jing / Yang, Chingwen / Birsoy, Kıvanç

The Journal of biological chemistry

2024 Volume 300, Issue 2, Page(s) 105645

Abstract: Glutathione (GSH) is a highly abundant tripeptide thiol that performs diverse protective and biosynthetic functions in cells. While changes in GSH availability are associated with inborn errors of metabolism, cancer, and neurodegenerative disorders, ... ...

Abstract	Glutathione (GSH) is a highly abundant tripeptide thiol that performs diverse protective and biosynthetic functions in cells. While changes in GSH availability are associated with inborn errors of metabolism, cancer, and neurodegenerative disorders, studying the limiting role of GSH in physiology and disease has been challenging due to its tight regulation. To address this, we generated cell and mouse models that express a bifunctional glutathione-synthesizing enzyme from Streptococcus thermophilus (GshF), which possesses both glutamate-cysteine ligase and glutathione synthase activities. GshF expression allows efficient production of GSH in the cytosol and mitochondria and prevents cell death in response to GSH depletion, but not ferroptosis induction, indicating that GSH is not a limiting factor under lipid peroxidation. CRISPR screens using engineered enzymes further revealed genes required for cell proliferation under cellular and mitochondrial GSH depletion. Among these, we identified the glutamate-cysteine ligase modifier subunit, GCLM, as a requirement for cellular sensitivity to buthionine sulfoximine, a glutathione synthesis inhibitor. Finally, GshF expression in mice is embryonically lethal but sustains postnatal viability when restricted to adulthood. Overall, our work identifies a conditional mouse model to investigate the limiting role of GSH in physiology and disease.
MeSH term(s)	Animals ; Mice ; Buthionine Sulfoximine/pharmacology ; Disease Models, Animal ; Glutamate-Cysteine Ligase/genetics ; Glutamate-Cysteine Ligase/metabolism ; Glutathione/metabolism ; Cell Line, Tumor ; Humans
Chemical Substances	Buthionine Sulfoximine (5072-26-4) ; Glutamate-Cysteine Ligase (EC 6.3.2.2) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2024.105645
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Article ; Online: Comparison of Dural Peeling versus Duraplasty for Surgical Treatment of Chiari Type I Malformation: Results and Complications in a Monocentric Patients' Cohort.

Del Gaudio, Nicole / Vaz, Geraldo / Duprez, Thierry / Raftopoulos, Christian

World neurosurgery

2018 Volume 117, Page(s) e595–e602

Abstract: Objective: Chiari malformation type I is typified by the downward herniation of the cerebellar tonsils through the foramen magnum, which can impede cerebrospinal fluid circulation and may lead to syringomyelia. The usual symptoms of this condition are ... ...

Abstract	Objective: Chiari malformation type I is typified by the downward herniation of the cerebellar tonsils through the foramen magnum, which can impede cerebrospinal fluid circulation and may lead to syringomyelia. The usual symptoms of this condition are neck pain and posterior headaches on Valsalva maneuver. Different surgical procedures have been described for cranio-cervical decompression (CCD), without a consensus being reached about the best suited technique. The primary end point of this study was to compare efficacy and complications rate of CCD using dural peeling (DPe) versus duraplasty (DP). The secondary end point was to find predictive factors of success of DPe. Methods: Twenty-eight consecutive patients with Chiari malformation type I (12 women and 16 men) requiring CCD were enrolled at our institution between August 2011 and November 2015. Ten patients (35.7%) underwent DP, and 18 (64.3%) DPe. A standardized magnetic resonance imaging protocol was performed before and at least 3 months after surgery. Symptomatic outcome was evaluated at the last follow-up visit. Results: Overall complications were more frequent in the DP (4 patients, 70%) group than in the DPe (none) group (P <0.05). All patients in the DP group improved clinically but only 12 patients (66.7%) in the DPe group (P = 0.1). Morphologic evolution at magnetic resonance imaging was similar in both groups. A moderate trend for changes in cerebellar tonsil conformation was shown in patients with clinical improvement (P = 0.07). Predictive factors of clinical improvement after DPe cannot be identified. Conclusions: CCD with DPe was less risky than with DP but had a lower responsive rate (66.7% vs. 100). Larger studies are therefore warranted to assess predictive factors of success of CCD with DPe.
MeSH term(s)	Adolescent ; Adult ; Arnold-Chiari Malformation/diagnostic imaging ; Arnold-Chiari Malformation/surgery ; Child ; Child, Preschool ; Decompression, Surgical ; Dura Mater/diagnostic imaging ; Dura Mater/surgery ; Female ; Follow-Up Studies ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Postoperative Complications/diagnostic imaging ; Young Adult
Language	English
Publishing date	2018-06-19
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2018.06.093
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Article: Suppression of epithelial proliferation and tumorigenesis by immunoglobulin A.

Donaldson, Gregory P / Reis, Gabriella L / Saad, Marwa / Mamede, Izabela / Chen, Guo / DelGaudio, Nicole L / Zhang, Dayu / Aydin, Begüm / Harrer, Caroline E / Castro, Tiago Br / Grivennikov, Sergei / Reis, Bernardo S / Stadtmueller, Beth M / Victora, Gabriel D / Mucida, Daniel

bioRxiv : the preprint server for biology

2023

Abstract: Immunoglobulin A (IgA) is the most abundant antibody isotype produced across mammals and plays a specialized role in mucosal ... ...

Abstract	Immunoglobulin A (IgA) is the most abundant antibody isotype produced across mammals and plays a specialized role in mucosal homeostasis
Language	English
Publishing date	2023-10-10
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.10.06.561290
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Article ; Online: A JAK2/IDH1-mutant MPN clone unmasked by ivosidenib in an AML patient without antecedent MPN.

Xiao, Wenbin / Miles, Linde A / Bowman, Robert L / Durani, Vidushi / Tian, Helen S / DelGaudio, Nicole L / Mishra, Tanmay / Zhu, Menglei / Zhang, Yanming / Stump, Sarah E / Tallman, Martin S / Levine, Ross L / Cai, Sheng F

Blood advances

2020 Volume 4, Issue 23, Page(s) 6034–6038

MeSH term(s)	Clone Cells ; Glycine/analogs & derivatives ; Humans ; Isocitrate Dehydrogenase ; Janus Kinase 2/genetics ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Pyridines
Chemical Substances	Pyridines ; Isocitrate Dehydrogenase (EC 1.1.1.41) ; IDH1 protein, human (EC 1.1.1.42.) ; JAK2 protein, human (EC 2.7.10.2) ; Janus Kinase 2 (EC 2.7.10.2) ; ivosidenib (Q2PCN8MAM6) ; Glycine (TE7660XO1C)
Language	English
Publishing date	2020-12-07
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2020003326
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Zs.A 7153: Show issues

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Article ; Online: Genomics analysis of hexanoic acid exposure in Drosophila species.

Drum, Zachary A / Lanno, Stephen M / Gregory, Sara M / Shimshak, Serena J / Ahamed, Mukshud / Barr, Will / Bekele, Bethlehem / Biester, Alison / Castro, Colleen / Connolly, Lauren / DelGaudio, Nicole / Humphrey, William / Karimi, Helen / Karolczak, Sophie / Lawrence, Tay-Shaun / McCracken, Andrew / Miller-Medzon, Noah / Murphy, Leah / Park, Cameron /

Park, Sojeong / Qiu, Chloe / Serra, Kevin / Snyder, Gigi / Strauss, Alexa / Tang, Spencer / Vyzas, Christina / Coolon, Joseph D

G3 (Bethesda, Md.)

2021 Volume 12, Issue 1

Abstract: Drosophila sechellia is a dietary specialist endemic to the Seychelles islands that has evolved to consume the fruit of Morinda citrifolia. When ripe, the fruit of M. citrifolia contains octanoic acid and hexanoic acid, two medium-chain fatty acid ... ...

Abstract	Drosophila sechellia is a dietary specialist endemic to the Seychelles islands that has evolved to consume the fruit of Morinda citrifolia. When ripe, the fruit of M. citrifolia contains octanoic acid and hexanoic acid, two medium-chain fatty acid volatiles that deter and are toxic to generalist insects. Drosophila sechellia has evolved resistance to these volatiles allowing it to feed almost exclusively on this host plant. The genetic basis of octanoic acid resistance has been the focus of multiple recent studies, but the mechanisms that govern hexanoic acid resistance in D. sechellia remain unknown. To understand how D. sechellia has evolved to specialize on M. citrifolia fruit and avoid the toxic effects of hexanoic acid, we exposed adult D. sechellia, D. melanogaster and D. simulans to hexanoic acid and performed RNA sequencing comparing their transcriptional responses to identify D. sechellia specific responses. Our analysis identified many more genes responding transcriptionally to hexanoic acid in the susceptible generalist species than in the specialist D. sechellia. Interrogation of the sets of differentially expressed genes showed that generalists regulated the expression of many genes involved in metabolism and detoxification whereas the specialist primarily downregulated genes involved in the innate immunity. Using these data, we have identified interesting candidate genes that may be critically important in aspects of adaptation to their food source that contains high concentrations of HA. Understanding how gene expression evolves during dietary specialization is crucial for our understanding of how ecological communities are built and how evolution shapes trophic interactions.
MeSH term(s)	Animals ; Caproates/metabolism ; Caproates/toxicity ; Drosophila/physiology ; Drosophila melanogaster/genetics ; Genomics ; Species Specificity
Chemical Substances	Caproates ; hexanoic acid (1F8SN134MX)
Language	English
Publishing date	2021-10-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2629978-1
ISSN	2160-1836 ; 2160-1836
ISSN (online)	2160-1836
ISSN	2160-1836
DOI	10.1093/g3journal/jkab354
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Article ; Online: Plasmacytoid dendritic cell expansion defines a distinct subset of RUNX1-mutated acute myeloid leukemia.

Xiao, Wenbin / Chan, Alexander / Waarts, Michael R / Mishra, Tanmay / Liu, Ying / Cai, Sheng F / Yao, Jinjuan / Gao, Qi / Bowman, Robert L / Koche, Richard P / Csete, Isabelle S / DelGaudio, Nicole L / Derkach, Andriy / Baik, Jeeyeon / Yanis, Sophia / Famulare, Christopher A / Patel, Minal / Arcila, Maria E / Stahl, Maximilian /

Rampal, Raajit K / Tallman, Martin S / Zhang, Yanming / Dogan, Ahmet / Goldberg, Aaron D / Roshal, Mikhail / Levine, Ross L

Blood

2020 Volume 137, Issue 10, Page(s) 1377–1391

Abstract: Plasmacytoid dendritic cells (pDCs) are the principal natural type I interferon-producing dendritic cells. Neoplastic expansion of pDCs and pDC precursors leads to blastic plasmacytoid dendritic cell neoplasm (BPDCN), and clonal expansion of mature pDCs ... ...

Abstract	Plasmacytoid dendritic cells (pDCs) are the principal natural type I interferon-producing dendritic cells. Neoplastic expansion of pDCs and pDC precursors leads to blastic plasmacytoid dendritic cell neoplasm (BPDCN), and clonal expansion of mature pDCs has been described in chronic myelomonocytic leukemia. The role of pDC expansion in acute myeloid leukemia (AML) is poorly studied. Here, we characterize patients with AML with pDC expansion (pDC-AML), which we observe in ∼5% of AML cases. pDC-AMLs often possess cross-lineage antigen expression and have adverse risk stratification with poor outcome. RUNX1 mutations are the most common somatic alterations in pDC-AML (>70%) and are much more common than in AML without pDC expansion and BPDCN. We demonstrate that pDCs are clonally related to, as well as originate from, leukemic blasts in pDC-AML. We further demonstrate that leukemic blasts from RUNX1-mutated AML upregulate a pDC transcriptional program, poising the cells toward pDC differentiation and expansion. Finally, tagraxofusp, a targeted therapy directed to CD123, reduces leukemic burden and eliminates pDCs in a patient-derived xenograft model. In conclusion, pDC-AML is characterized by a high frequency of RUNX1 mutations and increased expression of a pDC transcriptional program. CD123 targeting represents a potential treatment approach for pDC-AML.
MeSH term(s)	Adult ; Aged ; Blast Crisis/genetics ; Blast Crisis/pathology ; Core Binding Factor Alpha 2 Subunit/genetics ; Dendritic Cells/metabolism ; Dendritic Cells/pathology ; Female ; Humans ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/pathology ; Male ; Middle Aged ; Mutation
Chemical Substances	Core Binding Factor Alpha 2 Subunit ; RUNX1 protein, human
Language	English
Publishing date	2020-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2020007897
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Article ; Online: Leukemia Cell of Origin Influences Apoptotic Priming and Sensitivity to LSD1 Inhibition.

Cai, Sheng F / Chu, S Haihua / Goldberg, Aaron D / Parvin, Salma / Koche, Richard P / Glass, Jacob L / Stein, Eytan M / Tallman, Martin S / Sen, Filiz / Famulare, Christopher A / Cusan, Monica / Huang, Chun-Hao / Chen, Chun-Wei / Zou, Lihua / Cordner, Keith B / DelGaudio, Nicole L / Durani, Vidushi / Kini, Mitali / Rex, Madison /

Tian, Helen S / Zuber, Johannes / Baslan, Timour / Lowe, Scott W / Rienhoff, Hugh Y / Letai, Anthony / Levine, Ross L / Armstrong, Scott A

Cancer discovery

2020 Volume 10, Issue 10, Page(s) 1500–1513

Abstract: The cell of origin of oncogenic transformation is a determinant of therapeutic sensitivity, but the mechanisms governing cell-of-origin-driven differences in therapeutic response have not been delineated. Leukemias initiating in hematopoietic stem cells ( ...

Abstract	The cell of origin of oncogenic transformation is a determinant of therapeutic sensitivity, but the mechanisms governing cell-of-origin-driven differences in therapeutic response have not been delineated. Leukemias initiating in hematopoietic stem cells (HSC) are less sensitive to chemotherapy and highly express the transcription factor
MeSH term(s)	Apoptosis ; Gene Expression Regulation, Leukemic/genetics ; Histone Demethylases/antagonists & inhibitors ; Humans ; Leukemia/physiopathology ; Transcription Factors
Chemical Substances	Transcription Factors ; Histone Demethylases (EC 1.14.11.-) ; KDM1A protein, human (EC 1.5.-)
Language	English
Publishing date	2020-06-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2625242-9
ISSN	2159-8290 ; 2159-8274
ISSN (online)	2159-8290
ISSN	2159-8274
DOI	10.1158/2159-8290.CD-19-1469
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