Crossed Cerebellar Diaschisis Research Articles

Crossed Cerebellar Diaschisis and Cerebral Infarction After Cerebral Hyperperfusion Syndrome Following Carotid Artery Stenting: A Case Report

Crossed cerebellar diaschisis (CCD) often occurs after ischemic or hemorrhagic stroke that does great damage to the cortico-ponto-cerebellar pathway (CPCP). Nevertheless, as far as we know, CCD due to cerebral hyperperfusion syndrome (CHS) following carotid artery stenting (CAS) is rare. We report a case where CCD and new cerebral infarction after CHS following CAS was effectively treated by intravenous use of edaravone and mannitol. The patient was a 74-year-old female. She developed dizziness and vomiting accompanied with weakness of the right limb for 8 days and was admitted to our hospital. Computed tomography angiography scan revealed severe stenosis at the beginning of the left internal carotid artery. Further digital subtraction angiography (DSA) revealed severe stenosis at the beginning of the left internal carotid artery, with a stenosis rate of approximately 90%. Therefore, she underwent left CAS implantation. After the operation, the patient developed disturbance of consciousness and decreased muscle strength in the right limb. Intravenous infusion of edaravone and mannitol were then started. After 10 days of medical treatment, the condition of patient improved to mild hemiparesis. The findings in this present case strongly suggest that CHS after CAS for carotid artery stenosis may cause transient CCD.

Disability and persistent motor deficits are linked to structural crossed cerebellar diaschisis in chronic stroke.

Brain imaging has significantly contributed to our understanding of the cerebellum being involved in recovery after non-cerebellar stroke. Due to its connections with supratentorial brain networks, acute stroke can alter the function and structure of the contralesional cerebellum, known as crossed cerebellar diaschisis (CCD). Data on the spatially precise distribution of structural CCD and their implications for persistent deficits after stroke are notably limited. In this cross-sectional study, structural MRI and clinical data were analyzed from 32 chronic stroke patients, at least 6 months after the event. We quantified lobule-specific contralesional atrophy, as a surrogate of structural CCD, in patients and healthy controls. Volumetric data were integrated with clinical scores of disability and motor deficits. Diaschisis-outcome models were adjusted for the covariables age, lesion volume, and damage to the corticospinal tract. We found that structural CCD was evident for the whole cerebellum, and particularly for lobules V and VI. Lobule VI diaschisis was significantly correlated with clinical scores, that is, volume reductions in contralesional lobule VI were associated with higher levels of disability and motor deficits. Lobule V and the whole cerebellum did not show similar diaschisis-outcome relationships across the spectrum of the clinical scores. These results provide novel insights into stroke-related cerebellar plasticity and might thereby promote lobule VI as a key area prone to structural CCD and potentially involved in recovery and residual motor functioning.

Application study of DTI combined with ASL in the crossed cerebellar diaschisis after subacute cerebral hemorrhage.

To study the value of 3.0T magnetic resonance imaging with diffusion tensor imaging (DTI) and 3D-arterial spin labeling (ASL) perfusion imaging in the diagnosis of the crossed cerebellar diaschisis (CCD) after the unilateral supratentorial subacute cerebral hemorrhage. Fifty-eight patients with the unilateral supratentorial subacute cerebral hemorrhage who underwent diffusion tensor imaging (DTI), 3D-arterial spin labeling (ASL), and conventional magnetic resonance imaging (MRI) scanning were enrolled. Cerebral blood flow (CBF) values of the perihematomal edema (PHE) and bilateral cerebellar hemisphere were measured on ASL mapping, and the fractional anisotropy (FA) and mean diffusivity (MD) values of the bilateral cortical, pontine, and middle cerebellar peduncle (MCP) were measured on DTI mapping. In the CCD(+) group, FA values of the cerebral cortex and pontine ipsilateral to the lesion were statistically reduced compared to the contralateral side (P < 0.05), and the FA and MD values of the middle cerebellar peduncle (MCP) contralateral to the lesion were statistically reduced compared to the ipsilateral side (P < 0.05). Positive correlation was detected between the CBF values of the perihematomal edema (PHE) and the CBF values of cerebellar hemispheres (r = 0.642, P < 0.05), whereas the CBF values of PHE had a significantly high positive correlation with the FA in the contralateral MCP (r = 0.854, P < 0.05). CBF values in the contralateral cerebellar hemisphere correlated with FA (r = 0.466, P < 0.05) and MD values (r = 0.718, P < 0.05) in the contralateral MCP. Hemodynamic alterations of PHE and cortical-ponts-cerebellum (CPC) fibrous pathway damage are associated with the development of CCD; DTI technique can assess the degree of CPC fiber pathway injury at an early stage.

A Systematic Review of PET Contrasted with MRI for Detecting Crossed Cerebellar Diaschisis in Patients with Neurodegenerative Diseases.

There has not been extensive research into crossed cerebellar diaschisis (CCD) in neurodegenerative disorders. CCD is frequently detected using positron emission tomography (PET). However, advanced MRI techniques have come forth for the detection of CCD. The correct diagnosis of CCD is crucial for the care of neurological patients and those with neurodegenerative conditions. The purpose of this study is to determine whether PET can offer extra value over MRI or an advanced technique in MRI for detecting CCD in neurological conditions. We searched three main electronic databases from 1980 until the present and included only English and peer-reviewed journal articles. Eight articles involving 1246 participants met the inclusion criteria, six of which used PET imaging while the other two used MRI and hybrid imaging. The findings in PET studies showed decreased cerebral metabolism in the frontal, parietal, temporal, and occipital cortices, as on the opposite side of the cerebellar cortex. However, the findings in MRI studies showed decreased cerebellar volumes. This study concludes that PET is a common, accurate, and sensitive technique for detecting both crossed cerebellar and uncrossed basal ganglia as well as thalamic diaschisis in neurodegenerative diseases, while MRI is better for measuring brain volume. This study suggests that PET has a higher diagnostic value for diagnosing CCD compared to MRI, and that PET is a more valuable technique for predicting CCD.

Effects of intravascular photobiomodulation on cognitive impairment and crossed cerebellar diaschisis in patients with traumatic brain injury: a longitudinal study

The association between intravascular photobiomodulation (iPBM) and crossed cerebellar diaschisis (CCD) and cognitive dysfunction in patients with traumatic brain injury (TBI) remains unknown. We postulate that iPBM might enable greater neurologic improvements. The objective of this study was to evaluate the clinical impact of iPBM on the prognosis of patients with TBI. In this longitudinal study, patients who were diagnosed with TBI were recruited. CCD was identified from brain perfusion images when the uptake difference of both cerebella was > 20%. Thus, two groups were identified: CCD( +) and CCD( −). All patients received general traditional physical therapy and three courses of iPBM (helium–neon laser illuminator, 632.8 nm). Treatment assemblies were conducted on weekdays for 2 consecutive weeks as a solitary treatment course. Three courses of iPBM were performed over 2–3 months, with 1–3 weeks of rest between each course. The outcomes were measured using the Rancho Los Amigos Levels of Cognitive Functioning (LCF) tool. The chi-square test was used to compare categorical variables. Generalized estimating equations were used to verify the associations of various effects between the two groups. p < 0.05 indicated a statistically significant difference. Thirty patients were included and classified into the CCD( +) and CCD( −) groups (n = 15, each group). Statistics showed that before iPBM, CCD in the CCD( +) group was 2.74 (exp 1.0081) times higher than that of CCD( −) group (p = 0.1632). After iPBM, the CCD was 0.64 (exp-0.4436) times lower in the CCD( +) group than in the CCD( −) group (p < 0.0001). Cognitive assessment revealed that, before iPBM, the CCD( +) group had a non-significantly 0.1030 lower LCF score than that of CCD( −) group (p = 0.1632). Similarly, the CCD( +) group had a non-significantly 0.0013 higher score than that of CCD( −) after iPBM treatment (p = 0.7041), indicating no significant differences between the CCD( +) or CCD( −) following iPBM and general physical therapy. CCD was less likely to appear in iPBM-treated patients. Additionally, iPBM was not associated with LCF score. Administration of iPBM could be applied in TBI patients to reduce the occurrence of CCD. The study failed to show differences in cognitive function after iPBM, which still serves as an alternative non-pharmacological intervention.

Diaschisis Profiles in the Cerebellar Response to Hemodynamic Stimuli: Insights From Dynamic Measurement of Cerebrovascular Reactivity to Identify Occult and Transient Maxima.

Crossed cerebellar diaschisis (CCD) refers to depressions in perfusion and metabolism within the cerebellar hemisphere contralateral to supratentorial disease. Prior investigation into CCD in cerebrovascular reactivity (CVR) has been limited to terminal CVR estimations (CVRend ). We recently have demonstrated the presence of unsustained CVR maxima (CVRmax ) using dynamic CVR analysis, offering a fully dynamic characterization of CVR to hemodynamic stimuli. To investigate CCD in CVRmax from dynamic blood oxygen level-dependent (BOLD) MRI, by comparison with conventional CVRend estimation. Retrospective. A total of 23 patients (median age: 51 years, 10 females) with unilateral chronic steno-occlusive cerebrovascular disease, without prior knowledge of CCD status. A 3-T, T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) and acetazolamide-augmented BOLD imaging performed with a gradient-echo echo-planar imaging (EPI) sequence. A custom denoising pipeline was used to generate BOLD-CVR time signals. CVRend was established using the last minute of the BOLD response relative to the first-minute baseline. Following classification of healthy versus diseased cerebral hemispheres, CVRmax and CVRend were calculated for bilateral cerebral and cerebellar hemispheres. Three independent observers evaluated all data for the presence of CCD. Pearson correlations for comparing CVR across hemispheres, two-proportion Z-tests for comparing CCD prevalence, and Wilcoxon signed-rank tests for comparing median CVR. The level of statistical significance was set at P≤ 0.05. CCD-related changes were observed on both CVRend and CVRmax maps, with all CCD+ cases identifiable by inspection of either map. Diseased cerebral and contralateral cerebellar hemispheric CVR correlations in CCD+ patients were stronger when using CVRend (r=0.728) as compared to CVRmax (r=0.676). CVR correlations between healthy cerebral hemispheres and contralateral cerebellar hemispheres were stronger for CVRmax (r=0.739) than for CVRend (r=0.705). CCD-related alterations could be observed in CVR examinations. Conventional CVRend may underestimate CVR and could exaggerate CCD. 4. Stage 3.

Long-Term Lower Limb Motor Function Correlates with Middle Cerebellar Peduncle Structural Integrity in Sub-Acute Stroke: A ROI-Based MRI Cohort Study

Crossed cerebellar diaschisis (CCD) has been widely investigated in patients with supratentorial stroke. However, the role of CCD in lower limb recovery after stroke is still unknown. In this study, using a region-of-interest-based analysis of diffusion tensor imaging (DTI), a total of 44 cases of stroke within 3 months onset were enrolled for assessment of the cerebral peduncle (CP) and middle cerebellar peduncles (MCP) in CCD. Compared with the control group, the fractional anisotropy ratio (rFA) and laterality index (LI) of the CP and MCP in the stroke group significantly decreased. The rFA of the MCP (unaffected side/affected side) showed a more significant correlation with 1-year paresis grading (PG), lower extremity PG, upper extremity PG, National Institutes of Health Stroke Scale (NIHSS), and functional independence measure (FIM) motor item score, in comparison to the rFA of the CP (affected side/unaffected side) (r = -0.698 vs. r = -0.541, r = -0.651 vs. r = -0.386, r = -0.642 vs. r = -0.565, r = -0.519 vs. r = -0.403, and r = 0.487 vs. r = 0.435, respectively). Furthermore, the LI of the CP had a more significant association with 1-year Brunel Balance Assessment (BBA), upper extremity PG, and Modified Rankin Scale (mRS) as compared to the LI of the MCP (r = 0.573 vs. r = 0.452; r = -0.554 vs. r = -0.528; and r = -0.494 vs. r = -0.344, respectively). We set the cutoff point for the MCP rFA at 0.925 (sensitivity: 79% and specificity: 100%) for predicting lower extremity motor function prognosis and found the receiver operating characteristic (ROC) curve of MCP rFA was larger than that of CP rFA (0.893 vs. 0.737). These results reveal that the MCP may play a significant role in the recovery of walking ability after stroke.

Hypothermia increases cold-inducible protein expression and improves cerebellar-dependent learning after hypoxia ischemia in the neonatal rat.

Hypoxic ischemic encephalopathy remains a significant cause of developmental disability.1,2 The standard of care for term infants is hypothermia, which has multifactorial effects.3-5 Therapeutic hypothermia upregulates the cold-inducible protein RNA binding motif 3 (RBM3) that is highly expressed in developing and proliferative regions of the brain.6,7 The neuroprotective effects of RBM3 in adults are mediated by its ability to promote the translation of mRNAs such as reticulon 3 (RTN3).8 METHODS: Hypoxia ischemia or control procedure was conducted in Sprague Dawley rat pups on postnatal day 10 (PND10). Pups were immediately assigned to normothermia or hypothermia at the end of the hypoxia. In adulthood, cerebellum-dependent learning was tested using the conditioned eyeblink reflex. The volume of the cerebellum and the magnitude of cerebral injury were measured. A second study quantified RBM3 and RTN3 protein levels in the cerebellum and hippocampus collected during hypothermia. Hypothermia reduced cerebral tissue loss and protected cerebellar volume. Hypothermia also improved learning of the conditioned eyeblink response. RBM3 and RTN3 protein expression were increased in the cerebellum and hippocampus of rat pups subjected to hypothermia on PND10. Hypothermia was neuroprotective in male and female pups and reversed subtle changes in the cerebellum after hypoxic ischemic. Hypoxic ischemic produced tissue loss and a learning deficit in the cerebellum. Hypothermia reversed both the tissue loss and learning deficit. Hypothermia increased cold-responsive protein expression in the cerebellum and hippocampus. Our results confirm cerebellar volume loss contralateral to the carotid artery ligation and injured cerebral hemisphere, suggesting crossed-cerebellar diaschisis in this model. Understanding the endogenous response to hypothermia might improve adjuvant interventions and expand the clinical utility of this intervention.

Possible association of crossed cerebellar diaschisis with cerebellar ataxia in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

AbstractWe report a 50‐year‐old man with no history of stroke or migraine, who developed progressive gait ataxia and dementia. MRI showed diffuse leukoencephalopathy, multiple lacunar lesions, and cerebellar atrophy. Ischemic lesions were absent in the cerebellum. On SPECT, crossed cerebellar diaschisis (CCD) was seen. Genetic testing confirmed the diagnosis of cerebral autosomal‐dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with a heterozygous NOTCH3 mutation p.Arg182Cys. His cerebellar dysfunction may have been caused by CCD due to interruption of cerebral‐cerebellar connections. Our case showed that CCD could be important for cerebellar function in CADASIL.

Abstract 137: Diaschisis Profiles In The Hemodynamic Response To Hemodynamic Stimuli: Implications For Cerebellar Normalization In Patients With Steno-occlusive Disease

Introduction: Cerebellar hemispheres are commonly used as global references for internal normalization in hemodynamic analysis, including cerebrovascular reactivity (CVR) experiments. We have reported blood oxygen level-dependent (BOLD) MRI coupled acetazolamide for CVR; however, the influence of crossed cerebellar diaschisis (CCD) is understudied in this setting. Importantly, poor signal-to-noise traditionally limits BOLD-CVR to estimation of arbitrary exam conclusions (CVR end ). We developed a custom computational pipeline for dynamic CVR analysis, permitting unprecedented, dynamic maximal CVR (CVR max ) estimates. We describe CCD in a population of patients with chronic unilateral steno-occlusive disease (uSOD) using CVR max . Methods: 32 acetazolamide-challenge BOLD MRI exams in 23 patients with uSOD were examined using a custom denoising and preprocessing strategy for CVR time-signal analysis. BOLD pre and BOLD post were defined as the average of the respective first and last one-minute BOLD data. CVR end was calculated as %CVR=100*( BOLD post – BOLD pre )/ BOLD pre . CVR max was the maximal, denoised per-voxel value. CVR end and CVR max maps were produced. Cerebellar hemispheres ipsilateral and contralateral to the diseased cerebral hemisphere were visually compared for CCD. Pearson correlations were calculated to study CVR max and CVR end in cerebral and cerebellar hemispheres. Results: CCD could be observed in CVR end and CVR max maps (Figure 1). Significant correlations were observed between healthy cerebral and contralateral cerebellar hemispheres (r=0.5992, p=0.0011 for CVR max , r=0.5034, p=0.0054 for CVR end ). CVR max (r=0.4114, p=0.0215) but not CVR end (r=-0.085, p=0.6611) showed correlations between diseased cerebral and contralateral cerebellar hemispheres. Conclusion: We present novel CVR max estimation from dynamic BOLD-MRI, revealing CCD otherwise unrecognized by conventional BOLD-CVR.

Crossed Cerebellar Diaschisis Worsens the Clinical Presentation in Acute Large Vessel Occlusion

Introduction: Initial NIHSS in anterior large vessel occlusion (LVO) correlates partially with the hypoperfusion volume. We aimed at assessing the contribution of crossed cerebellar diaschisis (CCD) from the hypoperfused territory on LVO initial clinical deficit. Methods: CCD was retrospectively identified by brain CT perfusion imaging (CTP) in patients with anterior LVO treated by mechanical thrombectomy from January 2017 to July 2021. CCD was defined by CTP parameter alteration in the contralateral cerebellar hemisphere to the LVO. NIHSS, clinical/perfusion variables, and CCD were included in regression models to assess their interrelationships. Results: 206 patients were included. CCD was present in 90 patients (69%). NIHSS scores were higher on admission and at stroke discharge among patients with CCD (17.90 ± 6.1 vs. 11.4 ± 8.4, p < 0.001; 9.6 ± 7.7 vs. 6.6 ± 7.9, p = 0.049; respectively). Patients with a CCD had higher stroke volumes (118.2 ± 60.3 vs. 69.3 ± 59.7, p < 0.001) and lower rate of known atrial fibrillation (22% vs. 41%, p = 0.021). On multivariable logistic regression, CCD independently worsened the initial NIHSS (OR 4.85 [2.37–7.33]; p < 0.001). Conclusion: CCD is found in 69% of LVO on admission CTP, correlates with stroke volumes, and independently worsens initial NIHSS.

A subtle connection between crossed cerebellar diaschisis and supratentorial collateral circulation in subacute and chronic ischemic stroke

ObjectivesIt has not been reported whether collateral circulation, a factor closely related to the prognosis of patients with cerebral infarction, is related to the occurrence of crossed cerebellar diaschisis(CCD) or not. Our research attempts to verify the relationship between the collateral circulation grade and the occurrence of CCD, mainly by means of CTA and CTP. Materials and methodsA total of 47 patients were divided into a CCD-positive (Kim et al., 2019) or a CCD-negative group Furlanis et al. (2018) by calculating the asymmetry index (AI) value (<10%) of bilateral cerebellar cerebral blood flow (CBF). A 4-scale grading method was used to evaluate collateral circulation in the supratentorial infarct area, and the four perfusion parameters of the supratentorial and subtentorial brain regions were analyzed and compared between the two groups. The extent of vascular lesions was evaluated by MR sequences including DWI and MRA. ResultsAmong the four perfusion parameters, except for CBV, were significantly different between the bilateral cerebellum in the CCD-positive group, but only TTP in the supratentorial cerebral infarction area was statistically different in the two groups. Moreover, the collateral circulation sore in the CCD-positive group was significantly lower than that in the CCD-negative group. But no statistical difference was found in the comparison of DWI positive rates between the two groups. ConclusionThe collateral score in the supratentorial infarct area is correlated with the occurrence of CCD,which may be used to explain the effect of CCD on the prognosis of patients.

Lateralization of the crossed cerebellar diaschisis-associated metabolic connectivities in cortico-ponto-cerebellar and cortico-rubral pathways

This study aimed to explore the glucose metabolic profile of extrapyramidal system in patients with crossed cerebellar diaschisis (CCD). Furthermore, the metabolic connectivities in cortico-ponto-cerebellar and cortico-rubral pathways associated with CCD were also investigated. A total of 130 CCD positive (CCD+) and 424 CCD negative (CCD-) patients with unilateral cerebral hemisphere hypometabolism on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) were enrolled. Besides, the control group consisted of 56 subjects without any brain structural and metabolic abnormalities. Apart from the “autocorrelation”, metabolic connectivity pattern of right or left affected cerebellar hemisphere involved unilateral (left or right, respectively) caudate, pallidum, putamen, thalamus and red nucleus, in CCD+ patients with left or right supratentorial lesions, respectively (Puncorrected < 0.001, cluster size > 200). CCD+ group had significantly lower asymmetry index (AI) in cortico-ponto-cerebellar pathway (including ipsilateral cerebral white matter, ipsilateral pons, contralateral cerebellum white matter and contralateral cerebellum exterior cortex) and cortico-rubral pathway (including ipsilateral caudate, thalamus proper, pallidum, putamen, ventral diencephalon and red nucleus) than those of both CCD- and control groups (all P < 0.05). AI in contralateral cerebellum exterior cortex was significantly positively correlated with that in ipsilateral caudate, putamen, pallidum, thalamus proper, ventral diencephalon, red nucleus and pons among CCD+ group (all P < 0.01), but only with that in ipsilateral caudate and putamen among CCD- group (both P < 0.001). These results provide additional insight into the involvement of both cortico-ponto-cerebellar and cortico-rubral pathways in the presence of CCD, underlining the need for further investigation about the role of their aberrant metabolic connectivities in the associated symptoms of CCD.

Crossed cerebellar diaschisis-related supratentorial hemodynamic and metabolic status measured by PET/MR in assessing postoperative prognosis in chronic ischemic cerebrovascular disease patients with bypass surgery

ObjectiveCerebral ischemic status is an indicator of bypass surgery. Both hemodynamics and glucose metabolism are significant factors for evaluating cerebral ischemic status. The occurrence of crossed cerebellar diaschisis (CCD) is influenced by the degree of supra-tentorial perfusion and glucose metabolism reduction. This study aimed to investigate the relationship between the CCD-related supra-tentorial blood flow and metabolic status before bypass surgery in patients with chronic and symptomatic ischemic cerebrovascular disease and the prognosis of surgery.MethodsTwenty-four participants with chronic ischemic cerebrovascular disease who underwent hybrid positron emission tomography (PET)/magnetic resonance (MR) before bypass surgery were included. Arterial spin labeling (ASL)-MR and FDG-PET were used to measure blood flow and metabolism, respectively. The PET images were able to distinguish CCD. The supratentorial asymmetry index (AI) and volume in the decreased blood flow region, decreased metabolism region and co-decreased region on the affected side, except for the infarct area, were respectively obtained before bypass surgery. The neurological status was determined using the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores. Differences between CCD-positive (CCD +) and CCD-negative (CCD−) groups were investigated.ResultsFourteen (58%) of the 24 patients were diagnosed as CCD +. Before surgery, the NIHSS and mRS scores of the CCD + were significantly higher than those of the CCD− (1.0(1.0) vs. 0.0(1.0), P = 0.013; 1.0(1.5) vs. 0.0(1.5), P = 0.048). After the surgery, the NIHSS and mRS scores of the CCD + showed a significant decrease (0.0(1.0) to 0.0(0.0), P = 0.011; 0.0(0.5) to 0.0(0.0), P = 0.008). Significant differences were observed in the supra-tentorial decreased metabolism region (all Ps ≤ 0.05) between the CCD + and CCD− groups, but no differences were observed in the preprocedural decreased supratentorial blood flow region (P > 0.05). The preprocedural NIHSS score was strongly correlated with the metabolism AI value in the decreased metabolism region (r = 0.621, P = 0.001) and the co-decreased region (r = 0.571, P = 0.004).ConclusionsSupratentorial blood flow and metabolism are important indicators of CCD. This study showed that CCD + patients benefited more from bypass surgery than CCD− patients. Staging based on CCD-related supra-tentorial blood flow and metabolic status by hybrid PET/MR may help to personalize treatment.

Crossed cerebellar diaschisis in Alzheimer's disease.

Crossed cerebellar diaschisis (CCD) is characterized by hypometabolism and hypoperfusion on molecular imaging in the cerebellum due to a supratentorial lesion on the contralateral side. CCD is a well-established phenomenon in acute or subacute conditions such as infarction but it has been less well described in chronic conditions such as neurodegenerative dementias. Here, we investigate CCD in a large sample of 830 people meeting research criteria for Alzheimer's disease (AD) using [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET). This study is based on FDG-PET data collected at baseline as part of two large-scale Phase III clinical trials of a novel tau aggregation inhibitor medication, methylthioninium in mild to moderate AD participants. Quantification of FDG-PET hypometabolism was carried out using standardized uptake value ratio (SUVR), with the pons as the comparison region. SUVR was compared in different regions of interest between the right and left hemispheres of the brain and cerebellum in people with mild AD (Mini-Mental State Examination score ≥ 20). Comparison of SUVR in different brain regions demonstrated significant differences in the temporal, occipital and cerebellar cortices. Right and left asymmetry was noted with lower SUVR in the left temporal and occipital regions, whereas SUVR was lower in the right side of the cerebellum. Here, we found robust evidence of CCD in a large sample of people with AD, a chronic neurodegenerative condition. The presence of this phenomenon in AD opens up a new avenue of research in AD pathogenesis and has the potential to change future diagnostic and therapeutic strategies.

Voxel-based analysis of the metabolic asymmetrical and network patterns in hypermetabolism-associated crossed cerebellar diaschisis

Crossed cerebellar diaschisis (CCD) has been widely investigated in patients with supratentorial hypometabolism, however, the available evidence about the metabolic feature of CCD in patients with contralateral supratentorial hypermetabolism is lacking. This study aimed to assess the metabolic asymmetrical profile, network pattern and predisposing factors for the hypermetabolism-associated CCD, by using voxel-based asymmetry index (AI) and brain network analyses. Seventy CCD positive (CCD+) and 99 CCD negative (CCD-) patients with unilateral supratentorial hypermetabolism were introduced. Among different brain regions with AImax or AImin, striatum & thalamus was accompanied by the highest positive rate of CCD (85.7% or 70.1%, respectively). CCD+ group had significantly greater AImax (median [IQR], 0.62 [0.44–0.84] vs. 0.47 [0.35–0.61]), supratentorial hypermetabolic volume (1183.5 [399.3–3026.8] vs. 386.0 [152.0–1193.0]) and hypometabolic volume (37796.5 [24741.8–53278.0] vs. 3337.0 [1020.0–17193.0]), and lower AImin (−0.85 [-1.05–−0.73] vs. −0.49 [−0.68–−0.35]) compared with CCD- group (all P < 0.001). Logistic regression analysis manifested that patients with AImin located at striatum & thalamus were 16.4 times more likely to present CCD than those at frontal lobe (OR = 16.393; 95% CI, 4.463–60.207; P < 0.001), and the occurrence of CCD was also associated with AImax (OR = 49.594; 95% CI, 5.519–445.653; P < 0.001) and AImin (OR = 3.133 × 10−4, 95% CI, 1.693 × 10−5–5.799 × 10−3, P < 0.001). Brain network analysis indicated that the relative hypermetabolism in the contralateral supplementary motor cortex (SMC) and precuneus gyrus were constant in the CCD related patterns. These results demonstrated that the greater AImax, lower AImin and AImin located at striatum & thalamus should be predisposing factors for CCD in patients with unilateral supratentorial hypermetabolism. Relative increased activities in the contralateral SMC and precuneus gyrus might be attributed to a compensatory mechanism for the abnormal brain network related to CCD.

Evaluation of crossed cerebellar diaschisis after cerebral infarction in MCAO rats based on DKI.

To observe the expression of N-methyl-D-aspartate (NMDA), apoptosis and the effect on neurological function recovery in rat model with middle cerebral artery occlusion (MCAO). Diffusion kurtosis imaging (DKI) was used to evaluate crossed cerebellar diaschisis (CCD) and to provide experimental and theoretical basis for the clinical treatment. The MCAO models were established in rats. Eighty-four rats were randomly and evenly divided into 7groups, including control group, 6-h group, 12-h group, 24-h group, 48-h group, 7-day group and 14-day group. The rats were scanned by MRI at the above time points. Then, rats were sacrificed for H&E staining, immunohistochemical staining and TUNEL staining to detect the expression of NMDA in the core infarct area and cerebellum. At the end, the discussion of relationships between molecular biology and MRI parameters (ADC derived from DWI, and MD, MK and FA derived from DKI) was performed. The values of MD, ADC and FA in MCAO rats were all lower than those in the control group. All MRI parameters of the contralateral cerebellum were lower than those of the ipsilateral cerebellum (p<.05). The parameters reached the lowest value at 12h, except that the MK reached the highest at 12h. The expression of NMDA showed a fluctuation along time in the MCAO group. Overall, it is higher in the MCAO group than in the control group, reaching the maximum at 24h (p<.05). At the same time, the expression of NMDA in the contralateral cerebellum was higher than in the ipsilateral cerebellum. It is found that NMDA and DKI of CCD have the same changing trend, which indicates that the intervention of NMDA receptor apoptosis may become a new target for the treatment of cerebral infarction, and MRI parameters can predict the occurrence and development of CCD.

Crossed cerebellar diaschisis after acute ischemic stroke detected by intravoxel incoherent motion magnetic resonance imaging

To study the value of 3.0T magnetic resonance imaging with intravoxel incoherent motion (IVIM) in the diagnosis of the crossed cerebellar diaschisis (CCD) after the unilateral supratentorial acute ischemic stroke. Seventy-four patients with acute ischemic stroke who underwent intravoxel incoherent motion (IVIM), arterial spin labeling (ASL), and conventional magnetic resonance imaging (MRI) scanning were enrolled. Intravoxel incoherent motion-derived perfusion-related parameters including fast diffusion coefficient (D*), slow diffusion coefficient (D), vascular volume fraction (f), and arterial spin-labeling-derived cerebral blood flow (CBF) of bilateral cerebellum were measured. In the CCD-positive group, D*, D, and CBF values of the contralateral cerebellum decreased compared with those of the ipsilesional cerebellum (P < 0.05), whereas f significantly increased (P < 0.05). A positive correlation was detected between the slow diffusion coefficient-based asymmetry index (AI-D) and the cerebral blood flow-based asymmetry index (AI-CBF) (r = 0.515, P < 0.01), whereas the vascular volume fraction-based asymmetry index (AI-f) had a negative correlation with the cerebral blood flow-based asymmetry index (AI-CBF) (r = - 0.485, P < 0.01). Furthermore, the area under the receiver operating characteristic (ROC) curve value of AI-D and AI-f was 0.81 and 0.76, respectively. The IVIM is feasible for the detection of CCD. This technique might provide opportunities to further investigate the pathophysiology of CCD.

Crossed cerebellar diaschisis: risk factors and prognostic value in focal cortical dysplasia by 18F-FDG PET/CT.

Crossed cerebellar diaschisis (CCD) has been widely studied in hemispheric stroke but is less characterized in epilepsy. In this study, we used 18F-FDG PET/CT to investigate the risk factors for CCD and its prognostic value for intractable epilepsy caused by focal cortical dysplasia (FCD). One hundred medically intractable epilepsy patients pathologically diagnosed with FCD postoperatively were included and classified into two groups: CCD+ and CCD-. PET/CT images were analyzed qualitatively by visual assessment and semi-quantitatively using the absolute asymmetry index (|AI|). Clinical factors, including age, sex, body mass index (BMI), age at seizure onset, epilepsy duration, seizure type, seizure frequency, electroencephalography (EEG) and brain magnetic resonance imaging (MRI), were retrospectively assessed from medical records. Follow-up outcomes were evaluated according to the Engel classification at 3, 6, 12, 24 and 36months postoperatively. Of the 100 patients, 77 (77.0%) were classified as CCD-, and 23 (23.0%) were classified as CCD + . CCD+ patients had a higher number of lobes involved on PET (3.61 ± 2.16 vs 2.26 ± 1.01, P < 0.001) than CCD- patients. CCD- patients showed more negative MRI results than CCD + patients (P = 0.02). At 12months postoperatively, 70.7% (29/41) of CCD- patients and 30.8% (4/13) of CCD + patients presented a favourable prognosis (P = 0.02). Significant differences in the average |AI| values in the posterior frontal and anterior temporal lobes were found between CCD+ and CCD- patients (P < 0.05). The number of lobes involved on PET, structural anomalies on MRI, the |AI| values in the posterior frontal and anterior temporal lobes may be predisposing factors for CCD. CCD occurrence may help predict the prognosis of FCD patients at 12months postoperatively.

Crossed cerebellar diaschisis on 18F-FDG PET: Frequency across neurodegenerative syndromes and association with 11C-PIB and 18F-Flortaucipir

We used 18F-FDG-PET to investigate the frequency of crossed cerebellar diaschisis (CCD) in 197 patients with various syndromes associated with neurodegenerative diseases. In a subset of 117 patients, we studied relationships between CCD and cortical asymmetry of Alzheimer’s pathology (β-amyloid (11C-PIB) and tau (18F-Flortaucipir)). PET images were processed using MRIs to derive parametric SUVR images and define regions of interest. Indices of asymmetry were calculated in the cerebral cortex, basal ganglia and cerebellar cortex. Across all patients, cerebellar 18F-FDG asymmetry was associated with reverse asymmetry of 18F-FDG in the cerebral cortex (especially frontal and parietal areas) and basal ganglia. Based on our operational definition (cerebellar asymmetry >3% with contralateral supratentorial hypometabolism), significant CCD was present in 47/197 (24%) patients and was most frequent in corticobasal syndrome and semantic and logopenic variants of primary progressive aphasia. In β-amyloid-positive patients, mediation analyses showed that 18F-Flortaucipir cortical asymmetry was associated with cerebellar 18F-FDG asymmetry, but that cortical 18F-FDG asymmetry mediated this relationship. Analysis of 18F-FDG-SUVR values suggested that CCD might also occur in the absence of frank cerebellar 18F-FDG asymmetry due to symmetrical supratentorial degeneration resulting in a bilateral diaschisis process.