Pediatric postoperative cerebellar cognitive affective syndrome follows outflow pathway lesions

ObjectiveTo evaluate lesion location after pediatric cerebellar tumor resection in relation to the development of severe cognitive and affective disturbances, or cerebellar cognitive affective syndrome (CCAS).MethodsThe postsurgical lesion location of 195 pediatric patients with cerebellar tumors was mapped onto a template brain. Individuals with CCAS were matched to 2 participants without CCAS by sex, age, and lesion volume. Lesion analyses included both a hypothesis-driven evaluation of the cerebellar outflow pathway (deep nuclei and superior cerebellar peduncles) and data-driven multivariate lesion symptom mapping. Lesion-associated networks were evaluated by comparing connectivity patterns between the lesion location of cases with and those without CCAS with resting-state functional connectivity MRI data from large normative adult and pediatric cohorts.ResultsCCAS was present in 48 of 195 participants (24.6%) and was strongly associated with cerebellar outflow tract lesions (p < 0.0001). Lesion symptom mapping also highlighted the cerebellar outflow pathway, with peak findings in the fastigial nuclei extending into the inferior vermis. Lesion network mapping revealed that the cerebellar region most associated with CCAS was functionally connected to the thalamic mediodorsal nucleus, among other sites, and that higher connectivity between lesion location and the mediodorsal nucleus predicts CCAS occurrence (p < 0.01). A secondary analysis of 27 participants with mutism revealed similar localization of lesions and lesion-associated networks.ConclusionLesions of the cerebellar outflow pathway and inferior vermis are associated with major cognitive and affective disturbances after pediatric cerebellar tumor resection, and disrupted communication between the cerebellum and the thalamic mediodorsal nucleus may be important.

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Tractographic and Microstructural Analysis of the Dentato-Rubro-Thalamo-Cortical Tracts in Children Using Diffusion MRI

Cerebral Cortex ◽

10.1093/cercor/bhaa377 ◽

2020 ◽

Author(s):

Sebastian M Toescu ◽

Patrick W Hales ◽

Enrico Kaden ◽

Luis M Lacerda ◽

Kristian Aquilina ◽

...

Keyword(s):

Diffusion Mri ◽

Microstructural Analysis ◽

Tumor Resection ◽

Healthy Children ◽

Cerebellar Tumor ◽

Superior Cerebellar Peduncle ◽

Spherical Deconvolution ◽

Spherical Mean ◽

Cerebellar Peduncle ◽

Outflow Pathway

Abstract The dentato-rubro-thalamo-cortical tract (DRTC) is the main outflow pathway of the cerebellum, contributing to a finely balanced corticocerebellar loop involved in cognitive and sensorimotor functions. Damage to the DRTC has been implicated in cerebellar mutism syndrome seen in up to 25% of children after cerebellar tumor resection. Multi-shell diffusion MRI (dMRI) combined with quantitative constrained spherical deconvolution tractography and multi-compartment spherical mean technique modeling was used to explore the frontocerebellar connections and microstructural signature of the DRTC in 30 healthy children. The highest density of DRTC connections were to the precentral (M1) and superior frontal gyri (F1), and from cerebellar lobules I–IV and IX. The first evidence of a topographic organization of anterograde projections to the frontal cortex at the level of the superior cerebellar peduncle (SCP) is demonstrated, with streamlines terminating in F1 lying dorsomedially in the SCP compared to those terminating in M1. The orientation dispersion entropy of DRTC regions appears to exhibit greater contrast than that shown by fractional anisotropy. Analysis of a separate reproducibility cohort demonstrates good consistency in the dMRI metrics described. These novel anatomical insights into this well-studied pathway may prove to be of clinical relevance in the surgical resection of cerebellar tumors.

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B - 17Neuropsychological Recovery in a Pediatric Case of a Cerebellar Cognitive Affective Syndrome Status-Post Cerebellar Tumor Resection

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acy061.93 ◽

2018 ◽

Vol 33 (6) ◽

pp. 703-794

Author(s):

S Muslin ◽

S Peery ◽

H Aaron ◽

J Burciaga ◽

R Hirst

Keyword(s):

Tumor Resection ◽

Cerebellar Tumor ◽

Cerebellar Cognitive Affective Syndrome ◽

Pediatric Case

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Validity of Acute Stroke Lesion Volume Estimation by Diffusion-Weighted Imaging–Alberta Stroke Program Early Computed Tomographic Score Depends on Lesion Location in 496 Patients With Middle Cerebral Artery Stroke

Stroke ◽

10.1161/strokeaha.114.006694 ◽

2014 ◽

Vol 45 (12) ◽

pp. 3583-3588 ◽

Cited By ~ 22

Author(s):

Julian Schröder ◽

Bastian Cheng ◽

Martin Ebinger ◽

Martin Köhrmann ◽

Ona Wu ◽

...

Keyword(s):

Acute Stroke ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

Diffusion Weighted Imaging ◽

Volume Estimation ◽

Lesion Volume ◽

Lesion Location ◽

Computed Tomographic ◽

Stroke Lesion ◽

Middle Cerebral Artery Stroke

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A multivariate lesion symptom mapping toolbox and examination of lesion‐volume biases and correction methods in lesion‐symptom mapping

Human Brain Mapping ◽

10.1002/hbm.24289 ◽

2018 ◽

Vol 39 (11) ◽

pp. 4169-4182 ◽

Cited By ~ 28

Author(s):

Andrew T. DeMarco ◽

Peter E. Turkeltaub

Keyword(s):

Lesion Volume ◽

Lesion Symptom Mapping

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Anomaly detection in multimodal MRI identifies rare individual phenotypes among 20,000 brains

10.1101/2021.05.10.441017 ◽

2021 ◽

Author(s):

Zhiwei Ma ◽

Daniel S. Reich ◽

Sarah Dembling ◽

Jeff H. Duyn ◽

Alan P. Koretsky

Keyword(s):

White Matter ◽

Anomaly Detection ◽

Large Scale ◽

Mean Diffusivity ◽

Large Sample Size ◽

Lesion Volume ◽

Resting State Functional Connectivity ◽

Human Connectome Project ◽

Multimodal Mri ◽

Anomaly Score

The UK Biobank (UKB) is a large-scale epidemiological study and its imaging component focuses on the pre-symptomatic participants. Given its large sample size, rare imaging phenotypes within this unique cohort are of interest, as they are often clinically relevant and could be informative for discovering new processes and mechanisms. Identifying these rare phenotypes is often referred to as "anomaly detection", or "outlier detection". However, anomaly detection in neuroimaging has usually been applied in a supervised or semi-supervised manner for clinically defined cohorts of relatively small size. There has been much less work using anomaly detection on large unlabeled cohorts like the UKB. Here we developed a two-level anomaly screening methodology to systematically identify anomalies from ~19,000 UKB subjects. The same method was also applied to ~1,000 young healthy subjects from the Human Connectome Project (HCP). In primary screening, using ventricular, white matter, and gray matter-based imaging phenotypes derived from multimodal MRI, every subject was parameterized with an anomaly score per phenotype to quantitate the degree of abnormality. These anomaly scores were highly robust. Anomaly score distributions of the UKB cohort were all more outlier-prone than the HCP cohort of young adults. The approach enabled the assessments of test-retest reliability via the anomaly scores, which ranged from excellent reliability for ventricular volume, white matter lesion volume, and fractional anisotropy, to good reliability for mean diffusivity and cortical thickness. In secondary screening, the anomalies due to data collection/processing errors were eliminated. A subgroup of the remaining anomalies were radiologically reviewed, and a substantial percentage of them (UKB: 90.1%; HCP: 42.9%) had various brain pathologies such as masses, cysts, white matter lesions, infarcts, encephalomalacia, or prominent sulci. The remaining anomalies of the subgroup had unexplained causes and would be interesting for follow-up. Finally, we show that anomaly detection applied to resting-state functional connectivity did not identify any reliable anomalies, which was attributed to the confounding effects of brain-wide signal variation. Together, this study establishes an unsupervised framework for investigating rare individual imaging phenotypes within large heterogeneous cohorts.

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Association between lesion location and language function in adult glioma using voxel-based lesion-symptom mapping

NeuroImage Clinical ◽

10.1016/j.nicl.2015.10.010 ◽

2015 ◽

Vol 9 ◽

pp. 617-624 ◽

Cited By ~ 8

Author(s):

Pia Banerjee ◽

Kevin Leu ◽

Robert J. Harris ◽

Timothy F. Cloughesy ◽

Albert Lai ◽

...

Keyword(s):

Language Function ◽

Lesion Location ◽

Lesion Symptom Mapping ◽

Adult Glioma

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Agrammatism and Paragrammatism: A Cortical Double Dissociation Revealed by Lesion-Symptom Mapping

Neurobiology of Language ◽

10.1162/nol_a_00010 ◽

2020 ◽

Vol 1 (2) ◽

pp. 208-225 ◽

Cited By ~ 4

Author(s):

William Matchin ◽

Alexandra Basilakos ◽

Brielle C. Stark ◽

Dirk-Bart den Ouden ◽

Julius Fridriksson ◽

...

Keyword(s):

Speech Rate ◽

Region Of Interest ◽

Lesion Volume ◽

Double Dissociation ◽

High Resolution Mri ◽

Left Posterior ◽

Fundamental Distinction ◽

Secondary Analyses ◽

Lesion Symptom Mapping ◽

Left Hemisphere Stroke

The fundamental distinction of grammatical deficits in aphasia, agrammatism and paragrammatism, was made over a century ago. However, the extent to which the agrammatism/paragrammatism distinction exists independently of differences in speech fluency has not clearly been investigated. Despite much research on agrammatism, the lesion correlates of paragrammatism are essentially unknown. Lesion-symptom mapping was used to investigate the degree to which the lesion correlates of agrammatism and paragrammatism overlap or dissociate. Four expert raters assessed videos of 53 right-handed patients with aphasia following chronic left-hemisphere stroke retelling the Cinderella story. Consensus discussion determined each subject’s classification with respect to grammatical deficits as Agrammatic, Paragrammatic, Both, or No Grammatical Deficit. Each subject’s lesion was manually drawn on a high-resolution MRI and warped to standard space for group analyses. Lesion-symptom mapping analyses were performed in NiiStat including lesion volume as a covariate. Secondary analyses included speech rate (words per minute) as an additional covariate. Region of interest analyses identified a double dissociation between these syndromes: damage to Broca’s area was significantly associated with agrammatism, p = 0.001 (but not paragrammatism, p = 0.930), while damage to the left posterior superior and middle temporal gyri was significantly associated with paragrammatism, p < 0.001 (but not agrammatism, p = 0.873). The same results obtained when regressing out the effect of speech rate, and nonoverlapping lesion distributions between the syndromes were confirmed by uncorrected whole brain analyses. Our results support a fundamental distinction between agrammatism and paragrammatism.

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Impaired and preserved aspects of independent finger control in patients with cerebellar damage

Journal of Neurophysiology ◽

10.1152/jn.00142.2011 ◽

2012 ◽

Vol 107 (4) ◽

pp. 1080-1093 ◽

Cited By ~ 14

Author(s):

B. Brandauer ◽

J. Hermsdörfer ◽

T. Geißendörfer ◽

B. Schoch ◽

E. R. Gizewski ◽

...

Keyword(s):

Force Production ◽

Middle Finger ◽

Motor Command ◽

Cerebellar Tumor ◽

Cerebellar Damage ◽

Patient Groups ◽

Finger Forces ◽

Lesion Symptom Mapping ◽

Lift Off ◽

Finger Control

The influence of the cerebellum on independent finger control has rarely been investigated. We examined multidigit control in 22 patients with cerebellar degeneration, 20 patients with cerebellar stroke, and 21 patients with surgical lesions after cerebellar tumor removal. In the first task, either the index finger or the middle finger was actively lifted from an object during static holding. Both controls and cerebellar patients increased the forces of the nearby digits in synchrony with lift-off to maintain the total finger force. Patients used increased finger forces but showed no significant deficits in the pattern and timing of rearrangement of finger forces. In the second task, subjects had to press and release one finger against a force-sensitive keypad with the other fingers being inactive. All patient groups showed increased force production of the noninstructed (enslaved) fingers compared with controls. Lesion-symptom mapping in the focal patients revealed that lesions of the superior hand area were related to abnormal levels of enslaving. Increased finger forces in the finger-lifting task likely reflect an unspecific safety strategy. Increased effects of enslaving in the individuated key-press task, however, may be explained by a deterioration of cerebellar contribution to feedforward commands necessary to suppress activity in noninstructed fingers or by increased spread of the motor command intended for the instructed finger. Despite the large and diverse patient sample, surprisingly few abnormalities were observed. Both holding an object and finger typing are overlearned, automatized motor tasks, which may not or little depend on the integrity of the cerebellum.

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The link between resting-state functional connectivity and cognition in MS patients

Multiple Sclerosis Journal ◽

10.1177/1352458513495584 ◽

2013 ◽

Vol 20 (3) ◽

pp. 338-348 ◽

Cited By ~ 42

Author(s):

Álvaro J Cruz-Gómez ◽

Noelia Ventura-Campos ◽

Antonio Belenguer ◽

Cesar Ávila ◽

Cristina Forn

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Cognitive Status ◽

Control Group ◽

Cognitively Impaired ◽

Lesion Volume ◽

Resting State Functional Connectivity ◽

Frontoparietal Network ◽

Brain Parenchymal Fraction ◽

Brain Parenchymal

Objective: The objective of this paper is to explore differences in resting-state functional connectivity between cognitively impaired and preserved multiple sclerosis (MS) patients. Methods: Sixty MS patients and 18 controls were assessed with the Brief Repeatable Battery of Neuropsychological Tests (BRB-N). A global Z score of the BRB-N was obtained and allowed us to classify MS patients as cognitively impaired and cognitively preserved ( n = 30 per group). Functional connectivity was assessed by independent component analysis of resting-state networks (RSNs) related to cognition: the default mode network, left and right frontoparietal and salience network. Between-group differences were evaluated and a regression analysis was performed to describe relationships among cognitive status, functional connectivity and radiological variables. Results: Compared to cognitively preserved patients and healthy controls, cognitively impaired patients showed a lesser degree of functional connectivity in all RSNs explored. Cognitively preserved patients presented less connectivity than the control group in the left frontoparietal network. Global Z scores were positively and negatively correlated with brain parenchymal fraction and lesion volume, respectively. Conclusion: Decreased cognitive performance is accompanied by reduced resting state functional connectivity and directly related to brain damage. These results support the use of connectivity as a powerful tool to monitor and predict cognitive impairment in MS patients.

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