Another Piece of the Puzzle of Anomalous Connectivity in Joubert's Syndrome

AbstractWe report on the conventional and diffusion tensor imaging (DTI) findings of a 2-year-old child with clinical presentation of Joubert's Syndrome (JS) and brainstem structural abnormalities as depicted by neuroimaging.Conventional magnetic resonance imaging (MRI) showed a “molar tooth” configuration of the brainstem. A band-like formation coursing in an apparent axial plane anterior to the interpeduncular fossa was noted and appeared to partially cover the interpeduncular fossa.DTI maps and three-dimensional (3D) tractography demonstrated a prominent red-encoded white matter bundle anterior to the midbrain. Probable aberrant course of the bilateral corticospinal tracts (CST) was also depicted. Absence of the decussation of the superior cerebellar peduncles and elongated thickened, horizontal superior cerebellar peduncle (SCP) reflecting the molar tooth sign were also shown.Our report and the review of the published cases suggest that DTI and tractography may be very helpful to differentiate between interpeduncular heterotopias and similarly located white matter bundles corroborating the underlying etiology of axonal guidance disorders in the complex group of ciliopathies including JS. Our case represents an important additional puzzle piece to explore the variability of these ciliopathies.

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White matter differences between essential tremor and Parkinson disease

Neurology ◽

10.1212/wnl.0000000000006694 ◽

2018 ◽

Vol 92 (1) ◽

pp. e30-e39 ◽

Cited By ~ 5

Author(s):

Meher R. Juttukonda ◽

Giulia Franco ◽

Dario J. Englot ◽

Ya-Chen Lin ◽

Kalen J. Petersen ◽

...

Keyword(s):

White Matter ◽

Parkinson Disease ◽

Essential Tremor ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Superior Cerebellar Peduncle ◽

Radial Diffusivity ◽

Cerebellar Peduncles ◽

Cerebellar Peduncle

ObjectiveTo assess white matter integrity in patients with essential tremor (ET) and Parkinson disease (PD) with moderate to severe motor impairment.MethodsSedated participants with ET (n = 57) or PD (n = 99) underwent diffusion tensor imaging (DTI) and fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity values were computed. White matter tracts were defined using 3 well-described atlases. To determine candidate white matter regions that differ between ET and PD groups, a bootstrapping analysis was applied using the least absolute shrinkage and selection operator. Linear regression was applied to assess magnitude and direction of differences in DTI metrics between ET and PD populations in the candidate regions.ResultsFractional anisotropy values that differentiate ET from PD localize primarily to thalamic and visual-related pathways, while diffusivity differences localized to the cerebellar peduncles. Patients with ET exhibited lower fractional anisotropy values than patients with PD in the lateral geniculate body (p < 0.01), sagittal stratum (p = 0.01), forceps major (p = 0.02), pontine crossing tract (p = 0.03), and retrolenticular internal capsule (p = 0.04). Patients with ET exhibited greater radial diffusivity values than patients with PD in the superior cerebellar peduncle (p < 0.01), middle cerebellar peduncle (p = 0.05), and inferior cerebellar peduncle (p = 0.05).ConclusionsRegionally, distinctive white matter microstructural values in patients with ET localize to the cerebellar peduncles and thalamo-cortical visual pathways. These findings complement recent functional imaging studies in ET but also extend our understanding of putative physiologic features that account for distinctions between ET and PD.

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Smoothened and ARL13B are critical in mouse for superior cerebellar peduncle targeting

10.1101/2021.01.29.428892 ◽

2021 ◽

Author(s):

Sarah K. Suciu ◽

Alyssa B. Long ◽

Tamara Caspary

Keyword(s):

Axon Guidance ◽

Mouse Models ◽

Hedgehog Signaling ◽

Joubert Syndrome ◽

Molar Tooth ◽

Cerebellar Vermis ◽

Superior Cerebellar Peduncle ◽

Molar Tooth Sign ◽

Cerebellar Peduncles ◽

Cerebellar Peduncle

AbstractPatients with the ciliopathy Joubert syndrome present with physical anomalies, intellectual disability, and are diagnosed by the hindbrain “molar tooth sign” malformation. This radiological abnormality results from a combination of hypoplasia of the cerebellar vermis and inappropriate targeting of the white matter tracts of the superior cerebellar peduncles, which create a deepened interpeduncular fossa. ARL13B is a cilia-enriched regulatory GTPase established to regulate cell fate, cell proliferation and axon guidance through vertebrate Hedgehog signaling. In patients, point mutations in ARL13B cause Joubert syndrome. In order to understand the etiology of the molar tooth sign, we used mouse models to investigate the role of ARL13B during cerebellar development. We found ARL13B regulates superior cerebellar peduncle targeting and these fiber tracts require Hedgehog signaling for proper guidance. However, in mouse the Joubert-causing R79Q mutation in ARL13B does not disrupt Hedgehog signaling nor does it impact tract targeting. We found a small cerebellar vermis in mice lacking ARL13B function but no cerebellar vermis hypoplasia in mice expressing the Joubert-causing R79Q mutation. Additionally, mice expressing a cilia-excluded variant of ARL13B that transduces Hedgehog normally, showed normal tract targeting and vermis size. Taken together, our data indicate that ARL13B is critical for superior cerebellar peduncle targeting, likely via Hedgehog signaling, as well as control of cerebellar vermis size. Thus, our work highlights the complexity of ARL13B in molar tooth sign etiology.Summary statementJoubert syndrome is diagnosed by the hindbrain “molar tooth sign” malformation. Using mouse models, we show loss of the ciliary GTPase ARL13B, mutations in which lead to Joubert syndrome, result in two features of the molar tooth sign: hypoplasia of the cerebellar vermis and inappropriate targeting of the superior cerebellar peduncles. Furthermore, we demonstrate that loss of vertebrate Hedgehog signaling may be the underlying disrupted mechanism as we extend its role in axon guidance to the superior cerebellar peduncles.

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Genotype-associated cerebellar profiles in ALS: focal cerebellar pathology and cerebro-cerebellar connectivity alterations

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2021-326854 ◽

2021 ◽

pp. jnnp-2021-326854

Author(s):

Peter Bede ◽

Rangariroyashe H. Chipika ◽

Foteini Christidi ◽

Jennifer C. Hengeveld ◽

Efstratios Karavasilis ◽

...

Keyword(s):

White Matter ◽

Disease Burden ◽

Imaging Study ◽

Anterior Lobe ◽

Posterior Lobe ◽

Superior Cerebellar Peduncle ◽

Sporadic Als ◽

Cerebellar Peduncles ◽

Repeat Expansions ◽

Cerebellar Peduncle

ObjectiveCerebellar disease burden and cerebro-cerebellar connectivity alterations are poorly characterised in amyotrophic lateral sclerosis (ALS) despite the likely contribution of cerebellar pathology to the clinical heterogeneity of the condition.MethodsA prospective imaging study has been undertaken with 271 participants to systematically evaluate cerebellar grey and white matter alterations, cerebellar peduncle integrity and cerebro-cerebellar connectivity in ALS. Participants were stratified into four groups: (1) patients testing positive for GGGGCC repeat expansions in C9orf72, (2) patients carrying an intermediate-length repeat expansion in ATXN2, (3) patients without established ALS-associated mutations and (4) healthy controls. Additionally, the cerebellar profile of a single patient with ALS who had an ATXN2 allele length of 62 was evaluated. Cortical thickness, grey matter and white matter volumes were calculated in each cerebellar lobule complemented by morphometric analyses to characterise genotype-associated atrophy patterns. A Bayesian segmentation algorithm was used for superior cerebellar peduncle volumetry. White matter diffusivity parameters were appraised both within the cerebellum and in the cerebellar peduncles. Cerebro-cerebellar connectivity was assessed using deterministic tractography.ResultsCerebellar pathology was confined to lobules I–V of the anterior lobe in patients with sporadic ALS in contrast to the considerable posterior lobe and vermis disease burden identified in C9orf72 mutation carriers. Patients with intermediate ATXN2 expansions did not exhibit significant cerebellar pathology.ConclusionsFocal rather than global cerebellar degeneration characterises ALS. Pathognomonic ALS symptoms which are typically attributed to other anatomical regions, such as dysarthria, dysphagia, pseudobulbar affect, eye movement abnormalities and cognitive deficits, may be modulated, exacerbated or partially driven by cerebellar changes in ALS.

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Relationship between post-traumatic amnesia and white matter integrity in traumatic brain injury using tract-based spatial statistics

Scientific Reports ◽

10.1038/s41598-021-86439-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Min Jye Cho ◽

Sung Ho Jang

Keyword(s):

Traumatic Brain Injury ◽

White Matter ◽

Patient Group ◽

Injury Severity ◽

White Matter Integrity ◽

Superior Cerebellar Peduncle ◽

Uncinate Fasciculus ◽

Traumatic Amnesia ◽

Post Traumatic ◽

Cerebellar Peduncle

AbstractThis study used tract-based spatial statistics to examine the relationship between post-traumatic amnesia (PTA) and white matter integrity in patients with a traumatic brain injury (TBI). Forty-seven patients with TBI in the chronic stage and 47 age- and sex-matched normal control subjects were recruited to the study. Correlation coefficients were calculated to observe the relationships among the PTA duration, white matter fractional anisotropy (FA) values, and mini-mental state examination (MMSE) results in the patient group. Both before and after Benjamini–Hochberg (BH) corrections, FA values of 46 of the 48 regions of interests of the patient group were lower than those of the control group. The FA values of column and body of fornix, left crus of fornix, left uncinate fasciculus, right hippocampus part of cingulum, left medial lemniscus, right superior cerebellar peduncle, left superior cerebellar peduncle, and left posterior thalamic radiation (after BH correction: the uncinate fasciculus and right hippocampus part of cingulum) in the patient group were negatively correlated with PTA duration. PTA duration was related to the injury severity of eight neural structures, each of which is involved in the cognitive functioning of patients with TBI. Therefore, PTA duration can indicate injury severity of the above neural structures in TBI patients.

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Functional and structural MRI correlates of executive functions in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/13524585211033184 ◽

2021 ◽

pp. 135245852110331

Author(s):

Olga Marchesi ◽

Raffaello Bonacchi ◽

Paola Valsasina ◽

Paolo Preziosa ◽

Elisabetta Pagani ◽

...

Keyword(s):

Multiple Sclerosis ◽

Working Memory ◽

A Priori ◽

Structural Mri ◽

Wisconsin Card Sorting Test ◽

Cognitive Networks ◽

Superior Cerebellar Peduncle ◽

Card Sorting ◽

Cerebellar Peduncle ◽

Magnetic Resonance Imaging Mri

Background: Executive dysfunctions, including difficulties in attention, working memory, planning, and inhibition affect 15%–28% of multiple sclerosis (MS) patients. Objectives: To investigate structural and functional magnetic resonance imaging (MRI) abnormalities underlying executive function (EF) in MS patients. Methods: A total 116 MS patients and 65 controls underwent resting-state (RS) and diffusion-weighted sequences and neuropsychological examination, including Wisconsin Card Sorting Test (WCST) to test EF. Brain RS cognitive networks and fractional anisotropy (FA) from a priori selected white matter tracts were derived. Associations of WCST scores with RS functional connectivity (FC) and FA abnormalities were investigated. Results: In MS patients, predictors of working memory/updating were: lower corpus callosum (CC) FA, lower left working-memory network (WMN), right WMN RS FC for worse performance; lower executive control network (ECN), higher default-mode network (DMN), and salience network (SN) RS FC for better performance ( R2 = 0.35). Predictors of attention were lower CC genu FA, lower left WMN, and DMN RS FC for worse performance; higher left WMN and ECN RS FC for better performance ( R2 = 0.24). Predictors of worse shifting/inhibition were lower CC genu and superior cerebellar peduncle (SCP) FA, lower left WMN RS FC for worse performance; and higher ECN RS FC for better performance ( R2 = 0.24). Conclusions: CC and SCP microstructural damage and RS FC abnormalities in cognitive networks underlie EF frailty in MS.

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Are Anesthesia and Surgery during Infancy Associated with Decreased White Matter Integrity and Volume during Childhood?

Anesthesiology ◽

10.1097/aln.0000000000001808 ◽

2017 ◽

Vol 127 (5) ◽

pp. 788-799 ◽

Cited By ~ 10

Author(s):

Robert I. Block ◽

Vincent A. Magnotta ◽

Emine O. Bayman ◽

James Y. Choi ◽

Joss J. Thomas ◽

...

Keyword(s):

White Matter ◽

Mean Diffusivity ◽

White Matter Integrity ◽

Cerebral Peduncle ◽

Intracranial Volume ◽

Healthy Children ◽

Superior Cerebellar Peduncle ◽

Control Subjects ◽

Brain White Matter ◽

Cerebellar Peduncle

AbstractBackgroundAnesthetics have neurotoxic effects in neonatal animals. Relevant human evidence is limited. We sought such evidence in a structural neuroimaging study.MethodsTwo groups of children underwent structural magnetic resonance imaging: patients who, during infancy, had one of four operations commonly performed in otherwise healthy children and comparable, nonexposed control subjects. Total and regional brain tissue composition and volume, as well as regional indicators of white matter integrity (fractional anisotropy and mean diffusivity), were analyzed.ResultsAnalyses included 17 patients, without potential confounding central nervous system problems or risk factors, who had general anesthesia and surgery during infancy and 17 control subjects (age ranges, 12.3 to 15.2 yr and 12.6 to 15.1 yr, respectively). Whole brain white matter volume, as a percentage of total intracranial volume, was lower for the exposed than the nonexposed group, 37.3 ± 0.4% and 38.9 ± 0.4% (least squares mean ± SE), respectively, a difference of 1.5 percentage points (95% CI, 0.3 to 2.8; P = 0.016). Corresponding decreases were statistically significant for parietal and occipital lobes, infratentorium, and brainstem separately. White matter integrity was lower for the exposed than the nonexposed group in superior cerebellar peduncle, cerebral peduncle, external capsule, cingulum (cingulate gyrus), and fornix (cres) and/or stria terminalis. The groups did not differ in total intracranial, gray matter, and cerebrospinal fluid volumes.ConclusionsChildren who had anesthesia and surgery during infancy showed broadly distributed, decreased white matter integrity and volume. Although the findings may be related to anesthesia and surgery during infancy, other explanations are possible.

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Diffusion Tensor Imaging and Fiber Tractography

Handbook of Research on Advanced Techniques in Diagnostic Imaging and Biomedical Applications ◽

10.4018/978-1-60566-314-2.ch015 ◽

2009 ◽

pp. 229-246

Author(s):

Evanthia E. Tripoliti ◽

Dimitrios I. Fotiadis ◽

Konstantia Veliou

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Brain Regions ◽

Cerebral White Matter ◽

Tissue Microstructure ◽

Diffusion Weighted Images ◽

Fiber Tracts ◽

Diffusion Weighted ◽

Magnetic Resonance Imaging Mri

Diffusion Tensor Imaging (DTI) is a magnetic resonance imaging (MRI) modality which can significantly improve our understanding of the brain structures and neural connectivity. DTI measures are thought to be representative of brain tissue microstructure and are particularly useful for examining organized brain regions, such as white matter tract areas. DTI measures the water diffusion tensor using diffusion weighted pulse sequences which are sensitive to microscopic random water motion. The resulting diffusion weighted images (DWI) display and allow quantification of how water diffuses along axes or diffusion encoding directions. This can help to measure and quantify the tissue’s orientation and structure, making it an ideal tool for examining cerebral white matter and neural fiber tracts. In this chapter the authors discuss the theoretical aspects of DTI, the information that can be extracted from DTI data, and the use of the extracted information for the reconstruction of fiber tracts and the diagnosis of a disease. In addition, a review of known fiber tracking algorithms is presented.

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Severity of white matter hyperintensities: Lesion patterns, cognition, and microstructural changes

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x19893600 ◽

2019 ◽

Vol 40 (12) ◽

pp. 2454-2463 ◽

Cited By ~ 2

Author(s):

Weiyi Zeng ◽

Yaojing Chen ◽

Zhibao Zhu ◽

Shudan Gao ◽

Jianan Xia ◽

...

Keyword(s):

White Matter ◽

Episodic Memory ◽

Specific Pattern ◽

White Matter Hyperintensity ◽

Common Finding ◽

Superior Cerebellar Peduncle ◽

Brain White Matter ◽

Brain Microstructure ◽

Cerebellar Peduncle ◽

Fazekas Scale

White matter hyperintensity (WMH) is a common finding in aging population and considered to be a contributor to cognitive decline. Our study aimed to characterize the spatial patterns of WMH in different severities and explore its impact on cognition and brain microstructure in non-demented elderly. Lesions were both qualitatively (Fazekas scale) and quantitatively assessed among 321 community-dwelled individuals with MRI scanning. Voxel- and atlas-based analyses of the whole-brain white matter microstructure were performed. The WMH of the same severities was found to occur uniformly with a specific pattern of lesions. The severity of WMH had a significant negative association with the performance of working and episodic memory, beginning to appear in Fazekas 3 and 4. The white matter tracts presented significant impairments in Fazekas 3, which showed brain-wide changes above Fazekas 4. Lower FA in the superior cerebellar peduncle and left posterior thalamic radiation was mainly associated with episodic memory, and the middle cerebellar peduncle was significantly associated with working memory. These results support that memory is the primary domain to be affected by WMH, and the effect may potentially be influenced by tract-specific WM abnormalities. Fazekas scale 3 might be the critical stage predicting a future decline in cognition.

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Alternative Microstructural Measures to Complement Diffusion Tensor Imaging in Migraine Studies with Standard MRI Acquisition

Brain Sciences ◽

10.3390/brainsci10100711 ◽

2020 ◽

Vol 10 (10) ◽

pp. 711

Author(s):

Álvaro Planchuelo-Gómez ◽

David García-Azorín ◽

Ángel L. Guerrero ◽

Rodrigo de Luis-García ◽

Margarita Rodríguez ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Chronic Migraine ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Episodic Migraine ◽

Healthy Controls ◽

Axial Diffusivity ◽

Average Diffusion ◽

Cerebellar Peduncle

The white matter state in migraine has been investigated using diffusion tensor imaging (DTI) measures, but results using this technique are conflicting. To overcome DTI measures, we employed ensemble average diffusion propagator measures obtained with apparent measures using reduced acquisitions (AMURA). The AMURA measures were return-to-axis (RTAP), return-to-origin (RTOP) and return-to-plane probabilities (RTPP). Tract-based spatial statistics was used to compare fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity from DTI, and RTAP, RTOP and RTPP, between healthy controls, episodic migraine and chronic migraine patients. Fifty healthy controls, 54 patients with episodic migraine and 56 with chronic migraine were assessed. Significant differences were found between both types of migraine, with lower axial diffusivity values in 38 white matter regions and higher RTOP values in the middle cerebellar peduncle in patients with a chronic migraine (p < 0.05 family-wise error corrected). Significantly lower RTPP values were found in episodic migraine patients compared to healthy controls in 24 white matter regions (p < 0.05 family-wise error corrected), finding no significant differences using DTI measures. The white matter microstructure is altered in a migraine, and in chronic compared to episodic migraine. AMURA can provide additional results with respect to DTI to uncover white matter alterations in migraine.

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Progressive brain changes in schizophrenia: a 1-year follow-up study of diffusion tensor imaging

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2009.00422.x ◽

2009 ◽

Vol 21 (6) ◽

pp. 301-307 ◽

Cited By ~ 5

Author(s):

Miho Ota ◽

Satoko Obu ◽

Noriko Sato ◽

Katsuyoshi Mizukami ◽

Takashi Asada

Keyword(s):

Diffusion Tensor Imaging ◽

Diffusion Tensor ◽

Three Dimensional ◽

Anterior Cingulate ◽

Volume Data ◽

Cross Sectional ◽

Schizophrenic Patients ◽

Brain Changes ◽

Magnetic Resonance Imaging Mri

Objective:Recent cross-sectional studies suggest that brain changes in schizophrenia are progressive during the course of the disorder. However, it remains unknown whether this is a global process or whether some brain areas are affected to a greater degree. The aim of this study was to examine the longitudinal brain changes in patients with chronic older schizophrenia by magnetic resonance imaging (MRI).Methods:Three-dimensional (3D) T1-weighted and diffusion tensor (DT) MRI were performed twice on each of 16 chronic older schizophrenia patients (mean age = 58.1 ± 6.7 years ) with an interval of 1 year between imaging sessions. To clarify the longitudinal morphological and white matter changes, volume data and normalised diffusion tensor imaging (DTI) metrics were compared between the first and follow-up studies using a paired t-test.Results:Focal cortical volume loss was observed in the left prefrontal lobe and anterior cingulate on volumetric study. In addition, DTI metrics changed significantly at the bilateral posterior superior temporal lobes, left insula, genu of the corpus callosum and anterior cingulate.Conclusion:There are ongoing changes in the brains of schizophrenic patients during the course of the illness. Discrepancies between volume data and DTI metrics may indicate that the pattern of progressive brain changes varies according to brain region.

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