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Neurodevelopmental and Psychiatric Symptoms in Patients with a Cyst Compressing the Cerebellum: an Ongoing Enigma

  • Xavier GuellEmail author
  • Sheeba A. Anteraper
  • Satrajit S. Ghosh
  • John D. E. Gabrieli
  • Jeremy D. Schmahmann
Original Paper
  • 61 Downloads

Abstract

A patient diagnosed with developmental delay, intellectual disability, and autistic and obsessive-compulsive symptoms was found to have a posterior fossa arachnoid cyst (PFAC) compressing the cerebellum. The patient was referred to our Ataxia Unit for consideration of surgical drainage of the cyst to improve his clinical constellation. This scenario led to an in-depth analysis including a literature review, functional resting-state MRI analysis of our patient compared to a group of controls, and genetic testing. While it is reasonable to consider that there may be a causal relationship between PFAC and neurodevelopmental or psychiatric symptoms in some patients, there is also a nontrivial prevalence of PFAC in the asymptomatic population and a significant possibility that many PFAC are incidental findings in the context of primary cognitive or psychiatric symptoms. Our functional MRI analysis is the first to examine brain function, and to report cerebellar dysfunction, in a patient presenting with cognitive/psychiatric symptoms found to have a structural abnormality compressing the cerebellum. These neuroimaging findings are inherently limited due to their correlational nature but provide unprecedented evidence suggesting that cerebellar compression may be associated with cerebellar dysfunction. Exome gene sequencing revealed additional etiological possibilities, highlighting the complexity of this field of cerebellar clinical and scientific practice. Our findings and discussion may guide future investigations addressing an important knowledge gap—namely, is there a link between cerebellar compression (including arachnoid cysts and possibly other forms of cerebellar compression such as Chiari malformation), cerebellar dysfunction (including fMRI abnormalities reported here), and neuropsychiatric symptoms?

Keywords

Cerebellum fMRI Arachnoid cyst Neuropsychiatry Behavioral neurology 

Notes

Acknowledgments

This work was supported in part by the MINDlink foundation (JDS), La Caixa Banking Foundation (XG), MGH ECOR Fund for Medical Discovery Postdoctoral Fellowship Award (XG), and NIH grant R01 EB020740 (SSG). The control participant data collection was supported by the McGovern Institute Neurotechnology Fund and MIT Lincoln Laboratory. This research was carried out at the Athinoula A. Martinos Imaging Center at the McGovern Institute for Brain Research, Massachusetts Institute of Technology, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of MR instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program, specifically grant numbers S10RR022976 and S10RR019933. The authors want to thank Mathias Goncalves, Kevin R Sitek, Gregory Ciccarelli, Yoel Sanchez, Carlo de los Angeles, and Jakub R Kaczmarzyk for their participation in MRI control data collection.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest. JDS consults for Bayer, Biogen, Biohaven, and Cadent Pharmaceuticals and has no conflicts of interest to declare that may be perceived as biasing the content of this manuscript.

Supplementary material

12311_2019_1050_MOESM1_ESM.png (553 kb)
ESM 1 Top row: structural standard space (SPM single subject MNI brain) and its relationship with our cerebellum MVPA cluster (red). Bottom row: structural scan of the patient registered to standard space. While presence of the cyst is not eliminated from cerebellar territory (yellow arrow), our cerebellum MVPA cluster (red) is in lobules I-VI which were correctly registered (see cerebellar structures surrounding our MVPA cluster in the top and bottom images). MVPA findings are thus not a result of erroneous registration.(PNG 553 kb)
12311_2019_1050_Fig5_ESM.png (3.2 mb)
Fig. 5

Supplementary analysis repeating our main MVPA and post-hoc seed-to-voxel analyses including age and gender as additional regressors of no interest. The results of this supplementary analysis are virtually identical to those of our main analysis (compare panels a, b, and c here to panels a, b, and c of Figure 2), indicating that fMRI differences between our patient and controls as reported in our main analysis are not driven by age or gender.(PNG 3.17 mb)

12311_2019_1050_MOESM2_ESM.tif (3.2 mb)
Fig. 5

Supplementary analysis repeating our main MVPA and post-hoc seed-to-voxel analyses including age and gender as additional regressors of no interest. The results of this supplementary analysis are virtually identical to those of our main analysis (compare panels a, b, and c here to panels a, b, and c of Figure 2), indicating that fMRI differences between our patient and controls as reported in our main analysis are not driven by age or gender.(PNG 3.17 mb)

12311_2019_1050_MOESM3_ESM.png (7.9 mb)
ESM 3 Region-based volumetric analysis in our patient (red dots) compared to controls (black dots). Left: for each individual participant, each parcel’s volume is divided by the sum of all grey matter parcel’s volume, as a way to normalize for overall larger or smaller brain sizes between participants. Right: z scores in our patient and controls are shown for each parcel X as follows: ((normalized brain volume of X in one single participant) – (mean of normalized volume of X across all controls)) / (standard deviation of normalized volume of X across all controls). No differences between our patient and controls survived statistical significance testing (Crawford’s t-test, two-sided, with FDR correction for multiple comparisons and a threshold of p> 0.05). Abbreviations correspond to terminology of neuromorphometrics atlas (http://neuromorphometrics.com), as integrated in SPM’s CAT12 toolbox.(PNG 7.86 mb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Xavier Guell
    • 1
    • 2
    • 3
    Email author
  • Sheeba A. Anteraper
    • 1
    • 4
    • 5
  • Satrajit S. Ghosh
    • 1
    • 6
  • John D. E. Gabrieli
    • 1
  • Jeremy D. Schmahmann
    • 3
    • 7
  1. 1.McGovern Institute for Brain ResearchMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.Department of NeurologyHarvard Medical School and Massachusetts General HospitalCambridgeUSA
  3. 3.Laboratory for Neuroanatomy and Cerebellar Neurobiology, Department of Neurology, Massachusetts General HospitalHarvard Medical SchoolBostonUSA
  4. 4.Alan and Lorraine Bressler Clinical and Research Program for Autism Spectrum DisorderMassachusetts General HospitalBostonUSA
  5. 5.PEN LaboratoryNortheastern UniversityBostonUSA
  6. 6.Department of OtolaryngologyHarvard Medical SchoolBostonUSA
  7. 7.Ataxia Unit, Cognitive Behavioral Neurology Unit, Department of Neurology, Massachusetts General HospitalHarvard Medical SchoolBostonUSA

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