Hope Center member publications

List of publications for the week of July 27, 2021

Treatment strategies for hydrocephalus related to Dandy-Walker syndrome: Evaluating procedure selection and success within the Hydrocephalus Clinical Research Network” (2021) Journal of Neurosurgery: Pediatrics

Treatment strategies for hydrocephalus related to Dandy-Walker syndrome: Evaluating procedure selection and success within the Hydrocephalus Clinical Research Network
(2021) Journal of Neurosurgery: Pediatrics, 28 (1), pp. 93-101. 

Yengo-Kahn, A.M.a b , Wellons, J.C., IIIa b , Hankinson, T.C.c , Hauptman, J.S.d , Jackson, E.M.e , Jensen, H.f , Krieger, M.D.g , Kulkarni, A.V.h , Limbrick, D.D., Jr.i , McDonald, P.J.j , Naftel, R.P.a b , Pindrik, J.A.k , Pollack, I.F.l , Reeder, R.f , Riva-Cambrin, J.m , Rozzelle, C.J.n , Tamber, M.S.j , Whitehead, W.E.o , Kestle, J.R.W.p , Networkq

a Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, United States
b Surgical Outcomes Center for Kids, Monroe Carell Jr. Children’s Hospital, Vanderbilt University, Nashville, TN, United States
c Department of Neurosurgery, Children’s Hospital Colorado, Colorado Springs, CO, United States
d Department of Neurosurgery, Seattle Children’s Hospital, University of Washington, Seattle, WA, United States
e Department of Neurosurgery, The Johns Hopkins Hospital, Johns Hopkins University, Baltimore, MD, United States
f Department of Pediatrics, University of Utah, Salt Lake City, UT, United States
g Department of Neurosurgery, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA, United States
h Division of Neurosurgery, Hospital for Sick Children, Toronto, ON, Canada
i Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United States
j Division of Neurosurgery, British Columbia Children’s Hospital, The University of British Columbia, Vancouver, BC, Canada
k Department of Neurosurgery, The Ohio State University College of Medicine, Columbus, OH, United States
l Department of Neurosurgery, UPMC Children’s Hospital of Pittsburgh, University of PittsburghPA, United States
m Division of Neurosurgery Alberta Children’s Hospital, University of CalgaryAB, Canada
n Division of Neurosurgery, Children’s of Alabama, University of Alabama, Birmingham, AL, United States
o Department of Neurosurgery, Texas Children’s Hospital, Houston, TX, United States
p Department of Neurosurgery, University of Utah, Salt Lake City, UT, United States

Objective: Treating Dandy-Walker syndrome-related hydrocephalus (DWSH) involves either a CSF shunt-based or endoscopic third ventriculostomy (ETV)-based procedure. However, comparative investigations are lacking. This study aimed to compare shunt-based and ETV-based treatment strategies utilizing archival data from the Hydrocephalus Clinical Research Network (HCRN) registry. Methods: A retrospective review of prospectively collected and maintained data on children with DWSH, available from the HCRN registry (14 sites, 2008-2018), was performed. The primary outcome was revision-free survival of the initial surgical intervention. The primary exposure was either shunt-based (i.e., cystoperitoneal shunt [CPS], ventriculoperitoneal shunt [VPS], and/or dual-compartment) or ETV-based (i.e., ETV alone or with choroid plexus cauterization [CPC]) initial surgical treatment. Primary analysis included multivariable Cox proportional hazards models. Results: Of 8400 HCRN patients, 151 (1.8%) had DWSH. Among these, the 102 patients who underwent shunt placement (79 VPSs, 16 CPSs, 3 other, and 4 multiple proximal catheter) were younger (6.6 vs 18.8 months, p < 0.001) and more frequently had 1 or more comorbidities (37.3% vs 14.3%, p = 0.005) than the 49 ETV-treated children (28 ETVCPC). Fifty percent of the shunt-based and 51% of the ETV-based treatments failed. Notably, 100% (4/4) of the dualcompartment shunts failed. Adjusting for age, baseline ventricular size, and comorbidities, ETV-based treatment was not significantly associated with earlier failure compared with shunt-based treatment (HR for failure 1.32, 95% CI 0.77-2.26; p = 0.321). Complication rates were low: 4.9% and 6.1% (p = 0.715) for shunt- and ETV-based procedures, respectively. There was no difference in survival between ETV-CPC- and ETV-based treatment when adjusting for age (HR for failure 0.86, 95% CI 0.29-2.55, p = 0.783). Conclusions: In this North American, multicenter, prospective database review, shunt-based and ETV-based primary treatment strategies of DWSH appear similarly durable. Pediatric neurosurgeons can reasonably consider ETV-based initial treatment given the similar durability and the low complication rate. However, given the observational nature of this study, the treating surgeon might need to consider subgroups that were too small for a separate analysis. Very young children with comorbidities were more commonly treated with shunts, and older children with fewer comorbidities were offered ETV-based treatment. Future studies may determine preoperative characteristics associated with ETV treatment success in this population. © 2021 AANS.

Author Keywords
Dandy-Walker;  Endoscopic third ventriculostomy;  ETV;  Hydrocephalus clinical research network;  Posterior fossa cyst

Funding details
National Institute of Neurological Disorders and StrokeNINDS1RC1NS068943-01, 1U01NS107486-01A1
Gerber Foundation1692-3638
Patient-Centered Outcomes Research InstitutePCORICER-1403-13857
Hydrocephalus AssociationHA

Document Type: Article
Publication Stage: Final
Source: Scopus

Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia” (2021) Psychopharmacology

Brain volume in chronic ketamine users — relationship to sub-threshold psychotic symptoms and relevance to schizophrenia
(2021) Psychopharmacology, . 

Chesters, R.A.a b , Pepper, F.a b , Morgan, C.c , Cooper, J.D.a b d , Howes, O.D.a b e f , Vernon, A.C.a b f , Stone, J.M.a b e g h

a Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
b Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, SE5 8AF, United Kingdom
c University of Exeter, Exeter, United Kingdom
d Departments of Pediatrics, Genetics and Neurology, Medical School, Washington University in St Louis, 660S Euclid Ave, St Louis, MO 63110, United States
e South London and Maudsley NHS Trust, London, SE5 8AZ, United Kingdom
f MRC Centre for Neurodevelopmental Disorders, King’s College London, London, SE1 1UL, United Kingdom
g Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Falmer, BN1 9RY, United Kingdom
h Sussex Partnership NHS Foundation Trust, Eastbourne, BN21 2UD, United Kingdom

Rationale: Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis. Objectives: We tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic symptoms relative to a poly-drug user control group. Methods: Ketamine users (n = 17) and poly-drug using controls (n = 19) were included in the study. All underwent volumetric MRI imaging and measurement of sub-threshold psychotic symptoms using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Freesurfer was used to analyse differences in regional brain volume, cortical surface area and thickness between ketamine users and controls. The relationship between CAARMS ratings and brain volume was also investigated in ketamine users. Results: Ketamine users were found to have significantly lower grey matter volumes of the nucleus accumbens, caudate nucleus, cerebellum and total cortex (FDR p < 0.05; Cohen’s d = 0.36–0.75). Within the cortex, ketamine users had significantly lower grey matter volumes within the frontal, temporal and parietal cortices (Cohen’s d 0.7–1.31; FDR p < 0.05). They also had significantly higher sub-threshold psychotic symptoms (p < 0.05). Frequency of ketamine use showed an inverse correlation with cerebellar volume (p < 0.001), but there was no relationship between regional brain volumes and sub-threshold psychotic symptoms. Conclusions: Chronic ketamine use may cause lower grey matter volumes as well as inducing sub-threshold psychotic symptoms, although these likely arise through distinct mechanisms. © 2021, The Author(s).

Author Keywords
Brain volume;  Ketamine;  MRI;  Psychosis;  Schizophrenia

Funding details
Eli Lilly and Company
Medical Research CouncilMRCMC_A656_5QD30

Document Type: Article
Publication Stage: Article in Press
Source: Scopus