Cerebrospinal fluid and the early brain development of autism

Shen, Mark D.

doi:10.1186/s11689-018-9256-7

Cited by 62 publications

(46 citation statements)

References 79 publications

(139 reference statements)

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“…Nevertheless, it is still a matter of debate whether BBB dysfunction as measured with elevated AQs is the sequel of “leakage” at the site of small vessels and capillaries or a reduced CSF drainage in the context of disturbances of CSF flow [ 47 , 48 ]. For ASD, an altered CSF flow was suggested by Shen et al [ 29 ]. In their study of the MRIs of infants who later developed autism, the authors observed an increased extra-axial CSF volume as a possible sign of reduced CSF circulation [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…In patients, CSF analysis is the most precise method for investigating subtle inflammation in the central nervous system (CNS) [ 26 , 27 , 28 ]. Furthermore, there is evidence that CSF circulation, which usually supplies growth hormones and signal molecules and cleanses the brain of harmful substances for proper brain development, is impaired in ASD [ 29 ]. Earlier CSF studies in ASD have analyzed children and infants as well as post-mortem material but not adult patients.…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal Fluid Findings of 36 Adult Patients with Autism Spectrum Disorder

et al. 2020

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Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by difficulties with social interaction, repetitive behavior, and additional features, such as special interests. Its precise etiology is unclear. Recently, immunological mechanisms, such as maternal autoantibodies/infections, have increasingly been the subject of discussion. Cerebrospinal fluid (CSF) investigations play a decisive role in the detection of immunological processes in the brain. This study therefore retrospectively analyzed the CSF findings of adult patients with ASD. CSF basic measures (white blood cell count, total protein, albumin quotient, immunoglobulin G (IgG) index, and oligoclonal bands) and various antineuronal antibody findings of 36 adult patients with ASD, who had received lumbar puncture, were compared with an earlier described mentally healthy control group of 39 patients with idiopathic intracranial hypertension. CSF protein concentrations and albumin quotients of patients with ASD were significantly higher as compared to controls (age corrected: p = 0.003 and p = 0.004, respectively); 17% of the patients with ASD showed increased albumin quotients. After correction for age and gender, the group effect for total protein remained significant (p = 0.041) and showed a tendency for albumin quotient (p = 0.079). In the CSF of two ASD patients, an intrathecal synthesis of anti-glutamate decarboxylase 65 (GAD65) antibodies was found. In total, more of the ASD patients (44%) presented abnormal findings in CSF basic diagnostics compared to controls (18%; p = 0.013). A subgroup of the patients with adult ASD showed indication of a blood–brain barrier dysfunction, and two patients displayed an intrathecal synthesis of anti-GAD65 antibodies; thus, the role of these antibodies in patients with ASD should be further investigated. The results of the study are limited by its retrospective and open design. The group differences in blood–brain barrier markers could be influenced by a different gender distribution between ASD patients and controls.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Findings of 36 Adult Patients with Autism Spectrum Disorder

et al. 2020

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“…A prospective study was undertaken to evaluate brain growth trajectories from infancy in children who develop autism spectrum disorder. The presence of excessive extra‐axial fluid detected as early as 6 months with a lack of resolution by 24 months is a brain anomaly of infants who later develop autism spectrum disorder …”

Section: Clinical Implications and Future Perspectives On The Glymphamentioning

confidence: 99%

Glymphatic imaging using MRI

Taoka

Naganawa

2019

Magnetic Resonance Imaging

122

152

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FIGURE 6: Dynamic curves of relative signals after injection of 17O-labeled water. Dynamic curves of relative signal intensity. A bolus injection of saline or 17O was initiated 120 seconds after starting a scan. Significant drops in signal were observed in the cerebral cortex (a), choroid plexus (d), ventricle (e), and subarachnoid space (f) in the 17O condition, while only slight reductions in signal were noted in the basal ganglia/thalamus (b) and white matter (c). In the cerebral cortex, choroid plexus, and subarachnoid space, the curves are characterized by two phases: an initial signal drop and a plateau phase. In the ventricle, the signals gradually and continuously decreased during the acquisition window.

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“… Illustration of cerebrospinal fluid circulation in the ventricles, subarachnoid space surrounding the brain, interstitial space within the brain parenchyma, and draining into the meningeal lyphatic system and arachnoid granulations. Figure adapted with permission from Shen ( 2018 ). …”

Section: Introductionmentioning

confidence: 99%

A Novel Method for High-Dimensional Anatomical Mapping of Extra-Axial Cerebrospinal Fluid: Application to the Infant Brain

et al. 2020

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Cerebrospinal fluid (CSF) plays an essential role in early postnatal brain development. Extra-axial CSF (EA-CSF) volume, which is characterized by CSF in the subarachnoid space surrounding the brain, is a promising marker in the early detection of young children at risk for neurodevelopmental disorders. Previous studies have focused on global EA-CSF volume across the entire dorsal extent of the brain, and not regionally-specific EA-CSF measurements, because no tools were previously available for extracting local EA-CSF measures suitable for localized cortical surface analysis. In this paper, we propose a novel framework for the localized, cortical surface-based analysis of EA-CSF. The proposed processing framework combines probabilistic brain tissue segmentation, cortical surface reconstruction, and streamline-based local EA-CSF quantification. The quantitative analysis of local EA-CSF was applied to a dataset of typically developing infants with longitudinal MRI scans from 6 to 24 months of age. There was a high degree of consistency in the spatial patterns of local EA-CSF across age using the proposed methods. Statistical analysis of local EA-CSF revealed several novel findings: several regions of the cerebral cortex showed reductions in EA-CSF from 6 to 24 months of age, and specific regions showed higher local EA-CSF in males compared to females. These age-, sex-, and anatomically-specific patterns of local EA-CSF would not have been observed if only a global EA-CSF measure were utilized. The proposed methods are integrated into a freely available, open-source, cross-platform, user-friendly software tool, allowing neuroimaging labs to quantify local extra-axial CSF in their neuroimaging studies to investigate its role in typical and atypical brain development.

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Cerebrospinal fluid and the early brain development of autism

Cited by 62 publications

References 79 publications

Cerebrospinal Fluid Findings of 36 Adult Patients with Autism Spectrum Disorder

Cerebrospinal Fluid Findings of 36 Adult Patients with Autism Spectrum Disorder

Glymphatic imaging using MRI

A Novel Method for High-Dimensional Anatomical Mapping of Extra-Axial Cerebrospinal Fluid: Application to the Infant Brain

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