Cerebellar WM Research Articles

QSM-detected iron accumulation in the cerebellar gray matter is selectively associated with executive dysfunction in non-demented ALS patients.

This study aimed to assess whether quantitative susceptibility imaging (QSM)-based measures of iron accumulation in the cerebellum predict cognitive and behavioral features in non-demented amyotrophic lateral sclerosis (ALS) patients. A total of ALS patients underwent 3-T MRI and a clinical assessment using the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Regression models were applied to each subscale of the cognitive section of the ECAS and the ECAS-Carer Interview to examine the effect of QSM-based measures in white and gray matter (WM; GM) of the cerebellum, separately for right, left, and bilateral cerebellar regions of interest (ROIs). These effects were compared to those of cerebellar volumetrics in WM/GM, right and left hemispheres while controlling for demographics, disease status, and total intracranial volume. Higher QSM measures of the cerebellar GM on the left, right, and bilateral sides significantly predicted (ps ≤ 0.003) a greater number of errors on the executive functioning (EF) subscale of the ECAS (ECAS-EF). Moreover, higher GM-related, QSM measures of the cerebellum were associated with an increased probability of a below-cut-off performance on the ECAS-EF (ps ≤ 0.024). No significant effects were observed for QSM measures of the cerebellar WM or for volumetric measures on the ECAS-EF. Other ECAS measures showed no significant effects. Bilateral QSM measures of the cerebellar GM also selectively predicted performance on backward digit span and social cognition tasks. Iron accumulation within the cerebellar GM, particularly in the cerebellar cortices, may be associated with executive functioning deficits in non-demented ALS patients. Therefore, QSM-based measures could be useful for identifying the neural correlates of extra-motor cognitive deficits in ALS patients.

Mapping macrostructural and microstructural brain alterations in patients with neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a rare complex neurodegenerative disorder presents with various radiological features. The study aimed to investigate the structural abnormalities in NIID using multi-shell diffusion MR. Twenty-eight patients with adult-onset NIID and 32 healthy controls were included. Volumetric and diffusion MRI measures, including volume, fractional anisotropy (FA), mean diffusivity (MD), intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF) of six brain structures, including cortex, subcortical GM, cerebral WM, cerebellar GM and WM, and brainstem, were obtained and compared between NIID and healthy controls. Associations between MRI measures and clinical variables were investigated. Brain lesions of NIID included corticomedullary junction lesions on DWI, confluent leukoencephalopathy, lesions on callosum, cerebellar middle peduncle, cerebellar paravermal area and brainstem, and brain atrophy. Compared to healthy controls, NIID showed extensive volume loss of all the six brain regions (all p < 0.001); lower FA in cerebral WM (p < 0.001); higher MD in all WM regions; lower ODI in cortex (p < 0.001); higher ODI in subcortical GM (p < 0.001) and brainstem (p = 0.016); lower ICVF in brainstem (p = 0.001), and cerebral WM (p < 0.001); higher ISOVF in all the brain regions (p < 0.001). Higher MD of cerebellar WM was associated with worse cognitive level as evaluated by MoCA scores (p = 0.011). NIID patients demonstrated widespread brain atrophy but heterogeneous diffusion alterations. Cerebellar WM integrity impairment was correlated with the cognitive decline. The findings of the current study offer a sophisticated picture of brain structural alterations in NIID.

Associations of baseline and longitudinal change in cerebellum volume with age-related changes in verbal learning and memory

The cerebellum is involved in higher-order cognitive functions, e.g., learning and memory, and is susceptible to age-related atrophy. Yet, the cerebellum's role in age-related cognitive decline remains largely unknown. We investigated cross-sectional and longitudinal associations between cerebellar volume and verbal learning and memory. Linear mixed effects models and partial correlations were used to examine the relationship between changes in cerebellum volumes (total cerebellum, cerebellum white matter [WM], cerebellum hemisphere gray matter [GM], and cerebellum vermis subregions) and changes in verbal learning and memory performance among 549 Baltimore Longitudinal Study of Aging participants (2,292 visits). All models were adjusted by baseline demographic characteristics (age, sex, race, education), and APOE e4 carrier status. In examining associations between change with change, we tested an additional model that included either hippocampal (HC), cuneus, or postcentral gyrus (PoCG) volumes to assess whether cerebellar volumes were uniquely associated with verbal learning and memory. Cross-sectionally, the association of baseline cerebellum GM and WM with baseline verbal learning and memory was age-dependent, with the oldest individuals showing the strongest association between volume and performance. Baseline volume was not significantly associated with change in learning and memory. However, analysis of associations between change in volumes and changes in verbal learning and memory showed that greater declines in verbal memory were associated with greater volume loss in cerebellum white matter, and preserved GM volume in cerebellum vermis lobules VI-VII. The association between decline in verbal memory and decline in cerebellar WM volume remained after adjustment for HC, cuneus, and PoCG volume. Our findings highlight that associations between cerebellum volume and verbal learning and memory are age-dependent and regionally specific.

Volumetric MRI Changes in Spinocerebellar Ataxia (SCA3 and SCA10) Patients.

Spinocerebellar ataxias type 3 (SCA3) and type 10 (SCA10) are the most prevalent in southern Brazil. To analyze the relationships between volumetric MRI changes and clinical and genetic findings in SCA3 and SCA10 patients. All patients in the study had a confirmed genetic diagnosis. Demographic data, ataxia severity (SARA score), and the size of the expanded alleles were evaluated. Nineteen SCA3 and 18 SCA10 patients were selected and compared with a similar number of healthy controls. Patient and control groups underwent the same MRI protocol. The standard FreeSurfer pipeline was used for the morphometric data. Our results show more affected brain structures (volume reductions) in SCA3 patients than in SCA10 patients (15 vs. 5 structures). Volume reductions in brain structures were also greater in the former. The main areas with significant volumetric reductions in the former were the cerebellum, basal ganglia, brain stem, and diencephalon, whereas in the latter, significant volume reductions were observed in the cerebellum and pallidum. While SARA scores and disease duration were more correlated with volume reduction in SCA10, in SCA3, the expansion length (CAGn) correlated positively with cerebellar WM, thalamus, brain stem, and total GM volumes. There was no correlation between expansion length (ATTCTn) and neuroimaging findings in SCA10. Neuroimaging results differed significantly between SCA3 and SCA10 patients and were compatible with the differences in clinical presentation, disease progression, and molecular findings.

Atrophy of cerebellar peduncles in essential tremor: a machine learning-based volumetric analysis.

Subtle cerebellar signs are frequently observed in essential tremor (ET) and may be associated with cerebellar dysfunction. This study aims to evaluate the macrostructural integrity of the superior, middle, and inferior cerebellar peduncles (SCP, MCP, ICP) and cerebellar gray and white matter (GM, WM) volumes in patients with ET, and compare these volumes between patients with and without cerebellar signs (ETc and ETnc). Forty patients with ET and 37 age- and gender-matched healthy controls were recruited. Atlas-based region-of-interest analysis of the SCP, MCP, and ICP and automated analysis of cerebellar GM and WM volumes were performed. Peduncular volumes were employed in a multi-variate classification framework to attempt discrimination of ET from controls. Significant atrophy of bilateral MCP and ICP and bilateral cerebellar GM was observed in ET. Cerebellar signs were present in 20% of subjects with ET. Comparison of peduncular and cerebellar volumes between ETnc and ETc revealed atrophy of right SCP, bilateral MCP and ICP, and left cerebellar WM in ETc. The multi-variate classifier could discriminate between ET and controls with a test accuracy of 86.66%. Patients with ET have significant atrophy of cerebellar peduncles, particularly the MCP and ICP. Additional atrophy of the SCP is observed in the ETc group. These abnormalities may contribute to the pathogenesis of cerebellar signs in ET. • Patients with ET have significant atrophy of bilateral middle and inferior cerebellar peduncles and cerebellar gray matter in comparison with healthy controls. • Patients of ET with cerebellar signs have significant atrophy of right superior cerebellar peduncle, bilateral middle and inferior cerebellar peduncle, and left cerebellar white matter in comparison with ET without cerebellar signs. • A multi-variate classifier employing peduncular volumes could discriminate between ET and controls with a test accuracy of 86.66%.

Scaling of brain compartments to brain size.

In this study, we examine the relationship between total brain volume (BV) and the volumes of several main brain compartmental (BC) measures (cortical thickness, cortical surface area, corpus callosum, cortical gray matter, normal appearing cerebral white matter (NAWM), amygdala, accumbens, caudate, hippocampus, putamen, pallidum, thalamus, cerebellar gray matter, and cerebellar WM) of physically and cognitively healthy elderly individuals (mean age: 71 years, age range: 65-85 years). The statistical analysis uncovered extremely different relationships between total BV and the aforementioned BC metrics. These relationships ranged from extremely strong (BV explaining 85% of the variability of cerebral WM volume) to a very small relationship (for the caudate volume and the cortical thickness). In addition, cerebral WM and the accumbens volumes scaled out of proportion with BV, whereas most other BC measures scaled less than proportional to BV. Thus, larger brains exhibit relatively larger cerebral NAWM and accumbens volumes than do smaller brains. Cortical gray matter (and most other BC measures), on the other hand, relatively decreases as BV increases, resulting in relatively small cortical gray matter volumes (and relatively small BC measures) for large brains. These relationships are discussed within the context of general allometric scaling principles for the human brain. In addition, possible methodological consequences of analyzing anatomical data on the basis of MRI measurements are also discussed.

Cerebellar volume as imaging outcome in progressive multiple sclerosis.

Background and purposeTo assess whether cerebellar volumes changes could represent a sensitive outcome measure in primary-progressive MS.Material and methodsChanges in cerebellar volumes over one-year follow-up, estimated in 26 primary-progressive MS patients and 20 controls with Freesurfer longitudinal pipeline, were assessed using Wilcoxon test and tested for their correlation with disability worsening by a logistic regression. Clinical worsening was defined as EDSS score increase or change of >20% for 25-foot walk test or 9-hole peg test scores at follow-up. Sample sizes for given treatment effects and power were calculated. The findings were validated in an independent cohort of 20 primary-progressive MS patients.ResultsSignificant changes were detected in brain T1 lesion volume (p<0.01), cerebellar T2 and T1 lesion volume (p<0.01 and p<0.05), cerebellar volume, cerebellar cortex volume, and cerebellar WM volume (p<0.001). Only cerebellar volume and cerebellar cortex volume percentage change were significantly reduced in clinically progressed patients when compared to patients who did not progress (p<0.01; respectively AUC of 0.91 and 0.96). Cerebellar volume percentage changes were consistent in the exploration and validation cohorts (cerebellar volume -1.90±1.11% vs -1.47±2.30%; cerebellar cortex volume -1.68±1.41% vs -1.56±2.23%). Based on our results the numbers of patients required to detect a 30% effect are 81 per arm for cerebellar volume and 162 per arm for cerebellar cortex volume (90% power, type 1 error alpha = 0.05).ConclusionsOur results suggest a role for cerebellar cortex volume and cerebellar volume as potential short-term imaging metrics to monitor treatment effect in primary-progressive MS clinical trials.

Ataxia Severity Correlates with White Matter Degeneration in Spinocerebellar Ataxia Type 7.

There is a scarcity of information on the effect of white matter degeneration in patients with spinocerebellar ataxia type 7. Therefore, we investigated the WM integrity in a large group of patients with spinocerebellar ataxia type 7 by using Tract-Based Spatial Statistics. Thirty-three patients with a molecular diagnosis of spinocerebellar ataxia type 7 and their age- and sex-matched healthy controls participated in this study. The patients' ataxia severity was evaluated with the Scale for the Assessment and Rating of Ataxia. Voxelwise analyses of diffusion metrics, including fractional anisotropy and mean diffusivity, were performed with Tract-Based Spatial Statistics. The correlation between WM abnormalities and ataxia severity was then calculated. Tract-Based Spatial Statistics analysis revealed WM abnormalities in the cerebellum and the cerebellar peduncles, as well as in other major cortical and subcortical pathways. Further analysis between the Scale for the Assessment and Rating of Ataxia score and WM mean diffusivity showed significant associations only in key areas related to motor control and visuospatial processing, including the cerebellar WM, the middle occipital WM, the superior cerebellar peduncle, and bilateral anterior thalamic radiation. No significant associations between fractional anisotropy and the Scale for the Assessment and Rating of Ataxia were found. These results suggest a significant contribution of local cerebellar and cerebellar-midbrain connections to ataxic impairment in spinocerebellar ataxia type 7. The results also suggest an involvement of cortical WM abnormalities including tracts within the occipital and frontal cortices. These findings contribute to a more comprehensive view of the clinical impact of the white matter degeneration in spinocerebellar ataxia type 7.

Quiet T1-Weighted Pointwise Encoding Time Reduction with Radial Acquisition for Assessing Myelination in the Pediatric Brain.

T1-weighted pointwise encoding time reduction with radial acquisition (PETRA) sequences require limited gradient activity and allow quiet scanning. We aimed to assess the usefulness of PETRA in pediatric brain imaging. We included consecutive pediatric patients who underwent both MPRAGE and PETRA. The contrast-to-noise and contrast ratios between WM and GM were compared in the cerebellar WM, internal capsule, and corpus callosum. The degree of myelination was rated by using 4-point scales at each of these locations plus the subcortical WM in the anterior frontal, anterior temporal, and posterior occipital lobes. Two radiologists made all assessments, and the intra- and interrater agreement was calculated by using intraclass correlation coefficients. Acoustic noise on MPRAGE and PETRA was measured. We included 56 patients 5 days to 14 years of age (mean age, 36.6 months) who underwent both MPRAGE and PETRA. The contrast-to-noise and contrast ratios for PETRA were significantly higher than those for MPRAGE (P < .05), excluding the signal ratio for cerebellar WM. Excellent intra- and interrater agreement were obtained for myelination at all locations except the cerebellar WM. The acoustic noise on PETRA (58.2 dB[A]) was much lower than that on MPRAGE (87.4 dB[A]). PETRA generally showed better objective imaging quality without a difference in subjective image-quality evaluation and produced much less acoustic noise compared with MPRAGE. We conclude that PETRA can substitute for MPRAGE in pediatric brain imaging.

Cerebellar involvement in essential tremor with and without resting tremor: A Diffusion Tensor Imaging study

ObjectiveEssential Tremor with resting tremor (rET) is a debated and poorly understood clinical phenotype. Converging evidences show that neurodegeneration of the cerebellum underlies the pathophysiology of ET, but it is not known if cerebellar changes also occurs in patients with rET. The aim of our study was to evaluate cerebellar microstructure in patients with ET with- (rET) and without resting tremor (ETwr) in comparison to healthy controls by MR Diffusion Tensor Imaging (DTI). MethodsWe studied 67 patients with ET (rET: 29 and ETwr: 38) and 39 age-matched healthy controls (HC). DTI was performed to measure fractional anisotropy (FA) and mean diffusivity (MD) of white and grey matter (WM, GM) in the entire cerebellum and in right and left cerebellar hemispheres. ResultsMD was significantly higher in the cerebellar GM of ET total group (10.39 ± 0.87) in comparison with HC (9.90 ± 0.71) (p = 0.0027). Interestingly, MD was significantly different when ETwr (10.48 ± 0.77) were compared with HC (p = 0.0017), whereas a trend toward significance were found between rET (10.29 ± 0.99) and HC (p = 0.067). No differences among groups were found in MD of cerebellar WM and in FA values neither in the WM nor in the GM. ConclusionOur results demonstrate the presence of microstructural changes in the cerebellum of patients with ET. It is noteworthy that rET showed intermediate values compared to HC and ETwr, suggesting that rET shares part of the pathophysiological mechanisms of ETwr, but cerebellar involvement seems do not fully account for rET. In addition to the cerebellar loops, other networks may play a role in rET pathophysiology.

Mental health and cerebellar volume during adolescence in very-low-birth-weight infants: a longitudinal study.

BackgroundPreterm birth at very low birth weight (VLBW) poses a risk for cerebellar abnormalities and increased psychiatric morbidity compared with reference populations. We aimed to study cerebellar volumes (grey and white matter; GM, WM) and mental health in VLBW individuals and controls at 15 and 19 years of age, as well as changes between the two time points.MethodsForty VLBW (≤1500 g) and 56 control adolescents were included in the study at 15 years of age, and 44 VLBW and 60 control adolescents at 19 years of age. We had longitudinal data for 30 VLBW participants and for 37 controls. Clinical diagnoses were assessed following the schedule for affective disorders and schizophrenia for school-age children (KSADS). Psychiatric symptoms and function were further investigated with the Achenbach System of Empirically Based Assessment (ASEBA), ADHD Rating Scale-IV and the children’s global assessment scale (CGAS). An automatic segmentation of cerebellar GM and WM volumes was performed in FreeSurfer. The MRI scans were obtained on the same 1.5T scanner at both ages.ResultsThe VLBW group had higher rates of psychiatric disorders at both ages. Cerebellar growth trajectories did not differ between VLBW adolescents and controls, regardless of psychiatric status. However, VLBW adolescents who had a psychiatric diagnosis at both ages or developed a psychiatric disorder from 15 to 19 years had maintained smaller cerebellar WM and GM volumes than controls and also smaller volumes than VLWB adolescents who were or became healthy in this period. Moreover, there were no differences in cerebellar WM and GM volumes between controls and those VLBW who were healthy or became healthy. In the VLBW group, cerebellar WM and GM volumes correlated positively with psycho-social function at both 15 and 19 years of age, and smaller GM volumes were associated with inattention at 15 years.ConclusionsSmaller cerebellar volume in adolescents born very preterm and with VLBW may be a biomarker of increased risk of psychiatric problems in young adulthood.Electronic supplementary materialThe online version of this article (doi:10.1186/s13034-016-0093-8) contains supplementary material, which is available to authorized users.

PO-0005 Cerebellum, Thalamus And Cerebral Cortex In Vlbw Adolescents’ Mental Health

Background Children born preterm present a higher risk of psychiatric disorders during adolescence. Aim To assess whether psychiatric symptoms are associated with changes in cortical thickness and volumes of thalamus and cerebellum in very low birth weight (VLBW) adolescents. Design/methods Fifty VLBW (birth weight ≤1500 g) and 57 term control adolescents were assessed at 14–15 years of age with: Schedule for Affective Disorders and Schizophrenia for School-Age Children, Strengths and Difficulties Questionnaire (SDQ Mother Report), Autism Spectrum Screening Questionnaire (ASSQ), and Children’s Global Assessment Scale (CGAS). Cortical thickness (mm) and volumes of thalamus and cerebellum (ml) were obtained using an automated MRI segmentation technique (Freesurfer). Associations were analysed by linear and ordinal logistic regression, adjusted for age, gender and total intracranial volume, and corrected for multiple comparisons (Benjamini-Hochberg). Results VLBW adolescents had more psychiatric symptoms and diagnoses than controls. On MRI, they had several areas with thinner cortex, including the entorhinal cortex, and areas of thicker cortex, including the insula, compared to controls. Higher SDQ Emotional symptoms scores were associated with thicker insular cortex (Left: B=0.418 (0.192 to 0.644), p = 0.001; Right: B=0.243 (0.061 to 0.426), p = 0.010). Smaller cerebellar WM volumes were associated with higher SDQ Hyperactivity scores (Left: B=-0.638 (-1.101 to -0.176), p = 0.008; Right: B=-0.551 (-0.966 to -0.137), p = 0.010) and lower CGAS scores (Left: B=4.653 (2.182 to 7.123), p Conclusion Our results indicate that psychiatric symptoms in VLBW adolescents may be related to structural brain anomalies in cerebellar white matter and insular cortex.

Childhood Cerebral X-Linked Adrenoleukodystrophy: Diffusion Tensor Imaging Measurements for Prediction of Clinical Outcome after Hematopoietic Stem Cell Transplantation

DTI in cerebral X-linked adrenoleukodystrophy may demonstrate abnormalities in both affected and nonaffected WM; these values have not been studied serially after hematopoietic stem cell transplantation. The purpose of this study was to study pretransplant and posttransplant DTI parameters serially and ultimately to determine the ability of pretransplant DTI parameters to predict clinical outcome after HSCT in children with ALD. Eight patients with posterior-pattern cerebral ALD underwent DTI at 3T before HSCT (T0), at 30-60 days (T1), 90-120 days (T2), 180 days (T3), and 1 year (T4) after HSCT. FA and MD were serially measured in 19 regions, and these measurements were compared with those in control patients. MR imaging severity (Loes) scores were recorded. Correlations were performed between DTI parameters and Loes scores, neurologic function scores, and several neuropsychologic scores. Both FA and MD in subjects differed significantly from that in controls at nearly every time point within cerebellar WM, callosal splenium, and parieto-occipital WM; FA alone was significantly different at each time point within the optic radiations, lateral geniculate, and the Meyer loop (P < .05). Loes scores at T0 correlated strongly with each clinical score at T4 (r = 0.771-0.986, P < .05). The only significant DTI correlation at T0 with a clinical score at T4 was callosal body FA with adaptive function (r = 0.976, P < .001). Correlating the change in DTI values with change in NFS (change between T0 and T4) showed that only ΔMD within the optic radiations correlated strongly with ΔNFS (r = 0.903, P < .05). DTI values at T0 were generally poor predictors of outcome at 1 year, whereas Loes scores were generally good predictors. ΔMD within the optic radiations strongly correlates with ΔNFS over that year. In addition, certain normal-appearing regions, such as cerebellar WM, may have DTI abnormalities before HSCT that persist after HSCT.

MRI measures show significant cerebellar gray matter volume loss in multiple sclerosis and are associated with cerebellar dysfunction

Background Regional atrophy measures may offer useful information about the causes of specific clinical deficits in multiple sclerosis (MS). Objective To determine the magnitude of cerebellar gray and white matter (GM and WM) atrophy in patients with clinically isolated syndromes (CIS) and MS, and their role in clinical manifestations of cerebellar damage. Methods T1-weighted volumetric magnetic resonance imaging (MRI) of 73 patients [29 CIS, 33 relapsing–remitting MS (RRMS), 11 secondary progressive MS (SPMS)] was compared with 25 controls. GM and WM regions were generated using SPM5 and cerebellar regions delineated. Linear regression was used to investigate differences in tissue-specific cerebellar volumes between groups and the association with clinical measures. Results Mean cerebellar GM volume (CGMV) was 100.1 cm3 in controls, 96.4 cm3 in CIS patients, 91.8 cm3 in RRMS patients, and 88.8 cm3 in SPMS patients. Mean cerebellar WM volumes (CWMV) were 21.3 cm3, 20.4 cm3, 19.9 cm3, and 18.8 cm3, respectively. CGMV was reduced by 4.8 cm3 (P = 0.054) in RRMS patients, and 8.5 cm3 (P = 0.012) in SPMS patients, relative to controls. Only patients with SPMS showed a borderline significant reduction in CWMV compared with controls (mean 2.1 cm3, P = 0.053). CGMV was significantly smaller in patients assessed as having cerebellar dysfunction compared with patients who had normal cerebellar function. Significant associations of CGMV and CWMV with performance on the nine-hole peg test were also observed. Conclusion Clinically relevant GM atrophy occurs in the cerebellum of MS patients and is more prominent than WM atrophy. As such, it may provide complementary data to other regional atrophy and intrinsic tissue measures.