Larger Lesion Volumes Research Articles

Abstract TMP51: Association between genetic variation and acute stroke characteristics

Introduction: Strokes lead to acute deficits with wide-ranging severity. Genetic variation may explain some of these inter-subject differences. The current report examined the relationship that candidate genetic variants have with acute injury and acute behavioral deficits. We hypothesized that variants known to be associated with poorer stroke recovery would also be associated with more a severe acute presentation. Methods: Infarcts were outlined on clinical scans acquired during acute stroke admission as part of the STRONG (“Stroke, sTress, RehabilitatiON, and Genetics”) study and resampled to MNI152 brain standard space. Multivariable linear regression modeling was used to examine association with genetic measures known to be related to stroke outcome: 3 single nucleotide polymorphisms (SNPs): BDNF (rs6265), ACE (rs4291), and FAAH (rs324420), plus ApoE e4 and ApoE e2; a dopamine polygene score was also explored. Acute injury (infarct volume) and acute deficits (NIHSS score, grip strength, and acute stress disorder inventory (ASDI)) were each examined as the dependent measure in separate models that used age, gender, and ancestry as covariates. To understand where in the brain these relationships occurred, voxel lesion symptom mapping (VLSM) was used to test for associations between acute injury and each genetic measure. Results: In 448 subjects (age 63.4±14.4 yr (mean±SD), 43.1% females), lesion volume ranged from 0.46 to 535.13 cc and involved cortical grey matter in 63% of patients. Larger lesion volume was associated with presence of the ACE SNP (β=8.77, p=0.03); lower NIHSS score, with ApoE e4 (β=-1.69, p=0.04); greater grip strength, with ApoE e2 SNPs (β=6.78, p=0.03); and higher ASDI, with the ACE SNP (β=0.56, p=0.05). VLSM revealed that acute injury to the postcentral gyrus was significantly more likely in the presence of the ACE SNP (z=-3.5), and that acute injury to the calcarine fissure was significantly more likely in the presence of the BDNF SNP (z=-2.53). Conclusions: Genetic variants known to be associated with differences in stroke recovery are also related to acute stroke deficits and injury. In particular, a common variant in the gene for ACE was associated with differences in lesion volume and location, findings that may suggest a personalized medicine approach to acute therapy. Measures of genetic variability may be useful to understand inter-subject differences in acute injury and symptom severity, and may have therapeutic implications.

Acute Extrinsic Activation of the RANKL Pathway Decreases Wound Healing and Functional Recovery After Spinal Cord Injury in Mice.

Manipulating wound healing-associated signaling after SCI presents a promising avenue for increasing the recovery of function after injury. This study explores the potential of targeting molecular regulators of wound healing, initially identified in nonneural tissues, to enhance outcomes after SCI. Astrocytes, pivotal in central nervous system wound healing, play a crucial role in tissue remodeling and recovery. However, the optimal manipulation of astrogliosis for beneficial outcomes remains elusive. Previous research demonstrated a transcriptional response in astrocytes resembling epithelial-to-mesenchymal transitions (EMTs) after CNS injury. Here, we investigate the extrinsic manipulation of wound healing through the Receptor Activator of Nuclear-factor Kappa-Β (RANK) pathway, known for its involvement in nonneural tissue remodeling and linked to EMT pathway. Using a severe thoracic spinal cord contusion mouse model, we demonstrate that acute activation of the RANK pathway with RANK ligand (RANKL) adversely affects tissue remodeling, resulting in larger lesion volumes and delayed recovery of posture and locomotion. These findings suggest that early perturbations in the tight molecular regulation of tissue remodeling negatively impact the wound-healing process after SCI. The study provides a proof-of-concept demonstration that exogenous nonneural remodeling ligands can modify astrocyte responses and functional recovery after SCI, raising questions about the optimal time frame for beneficial remodeling interventions during injury progression. These insights open new avenues for therapeutic strategies aimed at improving functional outcomes following SCI.

Surgical Resection Followed by Stereotactic Radiosurgery (S+SRS) Versus SRS Alone for Large Posterior Fossa Brain Metastases: A Comparative Analysis of Outcomes and Factors Guiding Treatment Modality Selection.

Around 20% of cancer patients will develop brain metastases (BrMs), with 15-25% occurring in the posterior fossa (PF). Although the effectiveness of systemic therapies is increasing, surgery followed by stereotactic radiosurgery (S+SRS) versus definitive SRS remains the mainstay of treatment. Given the space restrictions within the PF, patients with BrMs in this location are at higher risk of brainstem compression, hydrocephalus, herniation, coma, and death. However, the criteria for treating large PF BrMs with S+SRS versus definitive SRS remains unclear. We reviewed a prospective registry database (2009 to 2020) and identified 64 patients with large PF BrMs (≥4 cc) treated with SRS or S+SRS. Clinical and radiological parameters were analyzed. The two endpoints were overall survival (OS) and local failure (LF). Patients in the S+SRS group were more highly symptomatic than patients in the SRS group. Gait imbalance and intracranial pressure symptoms were 97% and 80%, and 47% and 35% for S+SRS and SRS, respectively. Radiologically, there were significant differences in the mean volume of the lesions [6.7 cm3 in SRS vs. 29.8 cm3 in the S+SRS cohort, (p < 0.001)]; compression of the fourth ventricle [47% in SRS vs. 96% in S+SRS cohort, (p < 0.001)]; and hydrocephalus [0% in SRS vs. 29% in S+SRS cohort, (p < 0.001)]. Patients treated with S+SRS had a higher Graded Prognostic Assessment (GPA). LF was 12 and 17 months for SRS and S+SRS, respectively. Moreover, the S+SRS group had improved OS (12 vs. 26 months, p = 0.001). A higher proportion of patients treated with S+SRS presented with hydrocephalus, fourth-ventricle compression, and larger lesion volumes. SRS-alone patients had a lower KPS, a lower GPA, and more brain metastases. S+SRS correlated with improved OS, suggesting that it should be seriously considered for patients with large PF-BrM.

Spinal Cord Blood Perfusion Deficit is Associated with Clinical Impairment after Spinal Cord Injury.

Spinal cord injury (SCI) results in intramedullary microvasculature disruption and blood perfusion deficit at and remote from the injury site. However, the relationship between remote vascular impairment and functional recovery remains understudied. We characterized perfusion impairment invivo, rostral to the injury, using magnetic resonance imaging (MRI), and investigated its association with lesion extent and impairment following SCI. Twenty-one patients with chronic cervical SCI and 39 healthy controls (HC) underwent a high-resolution MRI protocol, including intravoxel incoherent motion (IVIM) and T2*-weighted MRI covering C1-C3 cervical levels, as well as T2-weighted MRI to determine lesion volumes. IVIM matrices (i.e., blood volume fraction, velocity, flow indices, and diffusion) and cord structural characteristics were calculated to assess perfusion changes and cervical cord atrophy, respectively. Patients with SCI additionally underwent a standard clinical examination protocol to assess functional impairment. Correlation analysis was used to investigate associations between IVIM parameters with lesion volume and sensorimotor dysfunction. Cervical cord white and gray matter were atrophied (27.60% and 21.10%, p < 0.0001, respectively) above the cervical cord injury, accompanied by a lower blood volume fraction (-22.05%, p < 0.001) and a higher blood velocity-related index (+38.72%, p < 0.0001) in patients with SCI compared with HC. Crucially, gray matter remote perfusion deficit correlated with larger lesion volumes and clinical impairment. This study shows clinically eloquent perfusion deficit rostral to a SCI, its magnitude driven by injury severity. These findings indicate trauma-induced widespread microvascular alterations beyond the injury site. Perfusion MRI matrices in the spinal cord hold promise as biomarkers for monitoring treatment effects and dynamic changes in microvasculature integrity following SCI.

Analysis of factors affecting pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound ablation: a retrospective study

Objectives To investigate all pregnancies and analyze the factors influencing pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound (HIFU). Materials and methods A total of 231 patients with adenomyosis who completed HIFU and wished to conceive were enrolled. The symptom improvement and information of pregnancy were recorded during the follow-up period. Factors influencing pregnancy outcomes were analyzed using multivariate regression analysis and survival analysis. Results After HIFU, 100 of 231 (43.3%) patients became pregnant within 96 months, including 77 (77/194, 39.7%) in natural and 23 (23/37, 62.2%) in vitro fertilization and embryo transfer (IVF-ET) pregnancies following gonadotropin-releasing hormone agonist (GnRHa). Among the 108 (46.8%, 108/231) infertile patients (defined as the failure to achieve pregnancy after 12 months of regular unprotected sexual intercourse, 40 primary infertility and 68 secondary infertility), 31 (28.7%) became pregnant. At the end of the follow-up, 70 successfully delivered 71 healthy babies. No uterine rupture occurred during pregnancy and delivery. Patients with pelvic adhesion and infertility history had a lower pregnancy chance than that of patients without pelvic adhesion and infertility history (OR < 1, p < 0.05). Patients with small adenomyotic lesion volume had a greater pregnancy chance than that of patients with large lesion volume (OR < 1, p < 0.05). IVF-ET following GnRHa had a better pregnancy chance (p < 0.05). Conclusions HIFU seems to have a beneficial effect on fertility of patients with adenomyosis. Pelvic adhesion, infertility history, and large adenomyotic lesion volume have adverse effects on pregnancy, but IVF-ET following GnRHa after HIFU could increase the pregnancy chance.

Resistin and In-Hospital Mortality in Patients with Acute Ischemic Stroke: A Prospective Study.

Background/Objectives: Understanding the prognostic factors of acute ischemic stroke (AIS) is essential for improving patient outcomes. The aim of this study was to establish the predictive role of plasmatic resistin and leptin on short-term mortality in adult patients with a first episode of AIS. Methods: This study enrolled 277 patients who were consecutively hospitalized for AIS. Demographic data, cardiovascular risk, comorbidities, and laboratory tests were collected. Death was noted if it occurred during hospitalization. Results: Death was recorded in 33 (11.9%) patients. Conducting multivariate analysis, the following variables were independent variables associated with in-hospital mortality: a resistin value of >11 ng/mL (OR 10.81 (95%CI 2.31;50.57), p = 0.002), a lesion volume of >18.8 mL (OR 4.87 (95%CI 1.87;12.67), p = 0.001), a NIHSS score of >7 (OR 5.88 (95%CI 2.01;17.16), p = 0.001), and the presence of IHD (OR 4.33 (95%CI 1.66;11.27), p = 0.003). This study has some limitations: single-center design (which may affect the generalizability of the results) and the potential impact of the COVID-19 pandemic on patient outcomes. Conclusions: This study demonstrated that resistin is a significant predictor of in-hospital mortality in AIS patients. Other established factors, such as a high NIHSS score, large lesion volume, and the presence of IHD, were reaffirmed as important predictors.

Volumetric and textural analysis of PET/CT in patients with diffuse large B-cell lymphoma highlights the importance of novel MTVrate feature.

To investigate the prognostic value of clinical, volumetric, and radiomics-based textural parameters in baseline [ 18 F]FDG-PET/CT scans of diffuse large B-cell lymphoma (DLBCL) patients. We retrospectively investigated baseline PET/CT scans and collected clinical data of fifty DLBCL patients. PET images were segmented semiautomatically to determine metabolic tumor volume (MTV), then the largest segmented lymphoma volume of interest (VOI) was used to extract first-, second-, and high-order textural features. A novel value, MTVrate was introduced as the quotient of the largest lesion's volume and total body MTV. Receiver operating characteristics (ROC) analyses were performed and 24-months progression-free survival (PFS) of low- and high-risk cohorts were compared by log-rank analyses. A machine learning algorithm was used to build a prognostic model from the available clinical, volumetric, and textural data based on logistic regression. The area-under-the-curve (AUC) on ROC analysis was the highest of MTVrate at 0.74, followed by lactate-dehydrogenase, MTV, and skewness, with AUCs of 0.68, 0.63, and 0.55, respectively which parameters were also able to differentiate the PFS. A combined survival analysis including MTV and MTVrate identified a subgroup with particularly low PFS at 38%. In the machine learning-based model had an AUC of 0.83 and the highest relative importance was attributed to three textural features and both MTV and MTVrate as important predictors of PFS. Individual evaluation of different biomarkers yielded only limited prognostic data, whereas a machine learning-based combined analysis had higher effectivity. MTVrate had the highest prognostic ability on individual analysis and, combined with MTV, it identified a patient group with particularly poor prognosis.

Characterization of Japanese multiple sclerosis patients with progression independent of relapse activity: A 2-year multicenter cohort study

Progression independent of relapse activity (PIRA) is prevalent among Caucasian patients with relapsing and remitting multiple sclerosis (RRMS). However, there is limited knowledge regarding the characteristics of PIRA in Asian patients with RRMS. Therefore, we retrospectively analyzed the clinical and radiological progression of 95 Japanese patients with RRMS during a 2-year observation period. PIRA was observed in three patients who were characterized by young age, large T2 lesion volume, and great reduction in brain volume. Despite having highly active disease, fewer patients with PIRA (33.3%) were treated with high-efficacy drugs compared with those without disease activity (60.7%).

The lesion core extent modulates the impact of early perfusion mismatch imaging on outcome variability after thrombectomy in stroke.

Despite profitable group effects on functional outcomes after mechanical thrombectomy (MT) in large vessel occlusion (LVO), many patients with successful reperfusion show a non-favorable long-term outcome, highlighting the necessity to identify potential biomarkers predicting outcome variability. In this regard, the role of perfusion mismatch imaging for outcome variability in the early time window within 6 h after symptom onset is a matter of debate. We attempted to investigate under which conditions early perfusion mismatch imaging accounts for variability in functional outcomes after mechanical thrombectomy. In a retrospective single-center study, we examined 190 consecutive patients with LVO who were admitted to the Medical Center Lübeck within 6 h after symptom onset, all of whom underwent MT. Perfusion mismatch was quantified by applying the Alberta Stroke Program Early CT score (ASPECTS) on CT-measured cerebral blood flow (CBF-ASPECTS) and subtracting it from an ASPECTS application on cerebral blood volume (CBV-ASPECTS), i.e., ASPECTS mismatch. Using multivariate ordinal regression models, associations between ASPECTS mismatch and modified Rankin Scale (mRS) after 90 days were assessed. Furthermore, the interaction between ASPECTS mismatch and the core lesion volume was calculated to evaluate conditional associations. ASPECTS mismatch did not correlate with functional outcomes when corrected for multiple influencing covariables. However, interactions between ASPECTS mismatch and CBV-ASPECTS [OR: 1.12 (1.06-1.18), p-value < 0.001], as well as NCCT-ASPECTS [OR: 1.15 (1.06-1.25), p-value < 0.001], did show a significant association with functional outcomes. Model comparisons revealed that, profoundly, in patients with large core lesion volumes (CBV-ASPECTS < 6 or NCCT-ASPECTS < 6), perfusion mismatch showed a negative correlation with the mRS. Perfusion mismatch imaging within the first 6 h of symptom onset provides valuable insights into the outcome variability of LVO stroke patients receiving thrombectomy but only in patients with large ischemic core lesions.

Association between renal insufficiency and lesion characteristics of posterior reversible encephalopathy syndrome.

Posterior reversible encephalopathy syndrome (PRES) is characterized by cerebral blood flow dysregulation and the blood-brain barrier (BBB) disruption. While renal insufficiency has been considered a factor in BBB fragility, the relationship between renal insufficiency and the PRES lesions volume remains unclear. This observational study was performed retrospectively. PRES patients were categorized into two groups with renal insufficiency, defined as an estimated glomerular filtration rate (eGFR) of less than 60mL/min/1.73m2 on the day of symptom occurrence. Lesion volume was measured using fluid-attenuated inversion recovery (FLAIR) imaging, and the brain was divided into nine regions. The volume of the parietal-occipital-temporal lobe was considered typical, while the other six regions were labeled as atypical. The study included 200 patients, of whom 94 (47%) had renal insufficiency. Patients with renal insufficiency had a larger lesion volume (144.7 ± 125.2cc) compared to those without renal insufficiency (110.5 ± 93.2cc; p = 0.032); particularly in the atypical lesions volume (49.2 ± 65.0 vs. 29.2 ± 44.3cc; p = 0.013). However, there was no difference in the reversibility of the lesions (35.2 ± 67.5 vs. 18.8 ± 33.4cc; p = 0.129). Multiple regression analysis revealed that decreases in eGFR (β = -0.34, 95% CI -0.62-0.05, p = 0.020) were positively associated with total lesion volume. Our findings suggest that PRES patients with renal insufficiency experience more severe lesion volumes, likely due to the atypical brain regions involvement. The lesions involving atypical regions may have a similar pathophysiology to typical lesions, as the PRES lesions reversibility was found to be similar between individuals with and without renal insufficiency.

Enhancing precision: A predictive model for 177Lu-DOTATATE treatment response in neuroendocrine tumors using quantitative 68Ga-DOTATATE PET and clinicopathological biomarkers.

Purpose: This study aims to elucidate the role of quantitative SSTR-PET metrics and clinicopathological biomarkers in the progression-free survival (PFS) and overall survival (OS) of neuroendocrine tumors (NETs) treated with peptide receptor radionuclide therapy (PRRT). Methods: A retrospective analysis including 91 NET patients (M47/F44; age 66 years, range 34-90 years) who completed four cycles of standard 177Lu-DOTATATE was conducted. SSTR-avid tumors were segmented from pretherapy SSTR-PET images using a semiautomatic workflow with the tumors labeled based on the anatomical regions. Multiple image-based features including total and organ-specific tumor volume and SSTR density along with clinicopathological biomarkers including Ki-67, chromogranin A (CgA) and alkaline phosphatase (ALP) were analyzed with respect to the PRRT response. Results: The median OS was 39.4 months (95% CI: 33.1-NA months), while the median PFS was 23.9 months (95% CI: 19.3-32.4 months). Total SSTR-avid tumor volume (HR = 3.6; P = 0.07) and bone tumor volume (HR = 1.5; P = 0.003) were associated with shorter OS. Also, total tumor volume (HR = 4.3; P = 0.01), liver tumor volume (HR = 1.8; P = 0.05) and bone tumor volume (HR = 1.4; P = 0.01) were associated with shorter PFS. Furthermore, the presence of large lesion volume with low SSTR uptake was correlated with worse OS (HR = 1.4; P = 0.03) and PFS (HR = 1.5; P = 0.003). Among the biomarkers, elevated baseline CgA and ALP showed a negative association with both OS (CgA: HR = 4.9; P = 0.003, ALP: HR = 52.6; P = 0.004) and PFS (CgA: HR = 4.2; P = 0.002, ALP: HR = 9.4; P = 0.06). Similarly, number of prior systemic treatments was associated with shorter OS (HR = 1.4; P = 0.003) and PFS (HR = 1.2; P = 0.05). Additionally, tumors originating from the midgut primary site demonstrated longer PFS, compared to the pancreas (HR = 1.6; P = 0.16), and those categorized as unknown primary (HR = 3.0; P = 0.002). Conclusion: Image-based features such as SSTR-avid tumor volume, bone tumor involvement, and the presence of large tumors with low SSTR expression demonstrated significant predictive value for PFS, suggesting potential clinical utility in NETs management. Moreover, elevated CgA and ALP, along with an increased number of prior systemic treatments, emerged as significant factors associated with worse PRRT outcomes.

Cognitive trajectory in the first year after first-ever ischaemic stroke in young adults: the ODYSSEY study

BackgroundLimited data exists on cognitive recovery in young stroke patients. We aimed to investigate the longitudinal course of cognitive performance during the first year after stroke at young age and...

PSV-5 Maternal Vitamin D Deficiency Increases the Incidence of Osteochondrotic-Like Lesions in the Distal Femur of Growing Pigs

Abstract The current objective was to evaluate the hypoviatminosis-D (Hypo-D) swine model for osteochondrosis-like (OC-like) lesions in the distal femur. Maternal and neonatal vitamin D deficient diets were used at specific production phases to produce OC-like lesions. Sows were fed 1 of 3 diets during gestation and lactation that included either 0 (GD-), 325 (GD+), or 1750 (GD++) IU D3/kg diet. Pigs produced by those sows were then fed 1 of 2 nursery diets for 4 weeks supplemented with either 0 (ND-) or 280 (ND+) IU D3/kg diet. After the nursery phase, all pigs were fed recovery diets formulated with 280 IU D3/kg. Dietary treatment groups included GD-ND- (n=16), GD+ND- (n=20), GD+ND+ (n=19), and GD++ND+ (n=15) for a total of 70 pigs. Pigs were euthanized at 22 weeks of age and the entire distal femoral joints were dissected for computed tomography (CT) scans and image analysis using Mimics (Materialize software, Version 23) to quantify whole-bone mineral volume (mm3), whole-bone mineral density (g/cm2), and OC-lesion characteristics across the physis and articular surfaces (number and volume of lesions). The incidence of kyphosis and distal femoral OC-like lesions were evaluated using binary count data (0 = no observations of spinal curvature or femoral OC-like lesions) or (1 = observations of spinal curvature or femoral OC-like lesions). Pigs in GD-ND- group did not recover body weight, whole-bone density, or whole-bone volume compared with pigs in other dietary treatment groups (P &amp;lt; 0.05; Table 1). The GD-ND- pigs had the greatest incidence of kyphosis (81%) and large physeal irregularities (LPI) in the distal femur (88%), compared with other groups. The distal femoral LPI in GD-ND- and GD+ND- groups had larger lesion volumes (P &amp;lt; 0.05) compared with pigs in GD+ND+ and GD++ND+ groups. However, small physeal lesions (SPL) and articular surface lesions (ASL) did not follow the same response pattern to dietary treatments. Interestingly, the GD+ND+ group had the largest volume of ASL compared with other groups (P &amp;lt; 0.05). The contrast in differential development of the three categories (SPL, ASL, and LPI) of lesions in the distal femur raises interesting questions about biological responses to vitamin D deficient diets at critical time points in long bone development. The present results infer that the time in which a vitamin D deficient diet is fed to sows and their subsequent offspring may alter the location, number, and size of OC-like lesions in the distal femur. Further studies are needed to fully characterize LPI and track the timing of a vitamin D deficiency with the different developmental growth patterns of the vertebral column and distal femur physis and articular surfaces.

Post-reperfusion acute MR diffusion in stroke is a potential predictor for clinical outcome in rats

Middle cerebral artery occlusion (MCAO) models show substantial variability in outcome, introducing uncertainties in the evaluation of treatment effects. Early outcome predictors would be essential for prognostic purposes and variability control. We aimed to compare apparent diffusion coefficient (ADC) MRI data obtained during MCAO and shortly after reperfusion for their potentials in acute-phase outcome prediction. Fifty-nine male rats underwent a 45-min MCAO. Outcome was defined in three ways: 21-day survival; 24 h midline-shift and neurological scores. Animals were divided into two groups: rats surviving 21 days after MCAO (survival group, n = 46) and rats dying prematurely (non-survival/NS group, n = 13). At reperfusion, NS group showed considerably larger lesion volume and lower mean ADC of the initial lesion site (p < 0.0001), while during occlusion there were no significant group differences. At reperfusion, each survival animal showed decreased lesion volume and increased mean ADC of the initial lesion site compared to those during occlusion (p < 10–6), while NS group showed a mixed pattern. At reperfusion, lesion volume and mean ADC of the initial lesion site were significantly associated with 24 h midline-shift and neurological scores. Diffusion MRI performed soon after reperfusion has a great impact in early-phase outcome prediction, and it works better than the measurement during occlusion.

Stroke Lesion Volume and Injury to Motor Cortex Output Determines Extent of Contralesional Motor Cortex Reorganization

Background After stroke, increases in contralesional primary motor cortex (M1CL) activity and excitability have been reported. In pre-clinical studies, M1CL reorganization is related to the extent of ipsilesional M1 (M1IL) injury, but this has yet to be tested clinically. Objectives We tested the hypothesis that the extent of damage to the ipsilesional M1 and/or its corticospinal tract (CST) determines the magnitude of M1CL reorganization and its relationship to affected hand function in humans recovering from stroke. Methods Thirty-five participants with a single subacute ischemic stroke affecting M1 or CST and hand paresis underwent MRI scans of the brain to measure lesion volume and CST lesion load. Transcranial magnetic stimulation (TMS) of M1IL was used to determine the presence of an electromyographic response (motor evoked potential (MEP+ and MEP−)). M1CL reorganization was determined by TMS applied to M1CL at increasing intensities. Hand function was quantified with the Jebsen Taylor Hand Function Test. Results The extent of M1CL reorganization was related to greater lesion volume in the MEP− group, but not in the MEP+ group. Greater M1CL reorganization was associated with more impaired hand function in MEP− but not MEP+ participants. Absence of an MEP (MEP−), larger lesion volumes and higher lesion loads in CST, particularly in CST fibers originating in M1 were associated with greater impairment of hand function. Conclusions In the subacute post-stroke period, stroke volume and M1IL output determine the extent of M1CL reorganization and its relationship to affected hand function, consistent with pre-clinical evidence. ClinicalTrials.gov Identifier: NCT02544503

Abstract TP84: Ring-like Pattern On Post-EVT MRI Is A Marker Of Perihematomal Edema

Introduction: Perihematomal edema is a consequence of primary intracerebral hemorrhage. On diffusion MRI, a corresponding heterogenous pattern of hypo- and hyper-intensity is visible on apparent diffusion coefficient (ADC), suggesting both cytotoxic and vasogenic edema. Analogously, endovascular therapy (EVT) for ischemic stroke can result in hemorrhagic transformation (HT) and a concomitant ring-like pattern, or “Rings” of mixed intensity on ADC. The objective of this study is to describe this pattern of secondary injury early after EVT. Methods: Patients were included if they consented to the prospective Natural History of Stroke GUARDS study from April 2018 to February 2022, were treated with EVT for anterior circulation LVO, achieved TICI 2b/3 reperfusion, and had early MRI, ~2h post-EVT. Two independent readers measured early and 24h DWI lesion volumes and 5d FLAIR lesion volumes using a semi-automated validated approach. Presence of any HT on GRE and Rings on ADC (Figure) on early, 24h, and 5d MRI were read independently by multiple readers who then reached consensus. The relationship of Rings with HT and lesion volume was explored. Results: Eighty-nine patients were included with median age 64y, 55% female, median admit NIHSS 18, 64% M1 LVO, and 47% IV tPA. On early MRI, 14 (16%) patients had Rings, 12 (86%) of whom also had HT (p&lt;0.001). At 24h, 42 (50%) patients had Rings with 33 (79%) also having HT (p&lt;0.001). There was a strong association between presence of Rings at 24h and 5d-FLAIR lesion volume, 56mL vs. 24mL in patients with vs. without Rings (p=0.002). Conclusions: Rings on ADC was seen in half of patients 24h post-EVT and appears to reflect peri-lesion edema associated with hemorrhagic transformation. This imaging marker was associated with larger lesion volumes at 5 days and may be able to serve as a target for adjunctive therapy post-EVT to mitigate edema formation.

The clinico-pathological characterization of Focal Cortical Dysplasia type IIb genetically defined by MTOR mosaicism.

Focal Cortical Dysplasia (FCD) is a major cause of drug-resistant paediatric epilepsy and is amenable to successful neurosurgical resection. FCD ILAE Type IIb is the most common FCD subtype, and brain somatic mutations affecting the mTOR pathway play a major pathogenic role. The aim of this study was to comprehensively describe the genotype-phenotype association of twenty patients with histopathologically confirmed FCDIIb using Next Generation Sequencing (NGS) of paired blood-brain samples METHODS: Clinical and neuropathological data were retrospectively reviewed from the hospital archive. The NGS panel included 11 mTOR-pathway-related genes with maximum coverage of 2000x. The detected variants were validated by digital droplet PCR. Pathogenic MTOR variants were identified in 10 patients (50%). Further comparison with MTOR-wildtype FCDIIb suggested a profound genotype-phenotype association characterized by (1) a non-temporal lobe lesion on MRI, (2) a larger lesion volume occupying grey and white matter (3.032±1.859cm3 vs. 1.110±0.856cm3 , p=0.014), (3) more balloon cells (50.20±14.40BC/mm2 vs. 31.64±30.56BC/mm2 , p=0.099) and dysmorphic neurons (48.72±19.47DN/mm2 vs. 15.28±13.95DN/mm2 , p=0.000), as well as (4) a positive correlation between VAF and the lesion volume (r=0.802, p=0.017). Our study identified frequent MTOR mutations in the cell-rich FCDIIb phenotype, clinically characterized by a non-temporal location and large lesion volume. Comprehensive genotype-phenotype associations will help us further explore and define the broad spectrum of FCD lesions to make more targeted therapies available in the realm of epileptology.

Buffer Coefficient as a Predictor of the Prognosis of Massive Cerebral Infarction

To evaluate the prognostic value of the buffer coefficient, calculated as the ratio of the buffer volume (volume of intracranial cerebrospinal fluid) at the peak of brain edema to the baseline brain volume, and some other parameters in patients with massive cerebral infarction (MCI). The cohort comprised 161 patients with MCI who were divided into good and poor prognosis groups according to modified Rankin Scale score at 90 days after onset. Differences in clinical and imaging parameters between these groups were analyzed by univariate analysis, and multifactorial binary logistic regression analysis was used to further identify influencing factors that were significantly different. Receiver operating characteristic curve was used to evaluate the diagnostic performance between the buffer volume and the buffer coefficient. The findings showed that a history of atrial fibrillation, intravenous tissue-type plasminogen activator administration, successful reperfusion, successful craniectomy, low-density lesion volume, brain volume, buffer volume, and buffer coefficient were significantly different between the poor and good prognosis groups (P < 0.05 for all comparisons). Multifactorial binary logistic regression analyses revealed that patients who had large low-density lesion volume and patients who had not achieved successful reperfusion or received intravenous tissue-type plasminogen activator were likely to have a poor prognosis (P < 0.05). The buffer coefficient was identified as an independent predictive factor for MCI (P < 0.001). The area under the receiver operating characteristic curve for the buffer coefficient was 0.862. When the cutoff value was 9.3%, sensitivity of predicting poor prognosis of patients with MCI was 94.7%. The buffer coefficient has potential benefits as a prognostic indicator for MCI that can be used to detect even subtle changes in brain edema.

15% of Talar Osteochondral Lesions Are Present Bilaterally While Only 1 in 3 Bilateral Lesions Are Bilaterally Symptomatic.

The primary aim of the present study was to determine the prevalence of osteochondral lesions of the contralateral talus in patients with computed tomography (CT)-confirmed osteochondral lesions of the talus (OLT). The secondary aims were to determine if the contralateral lesions were symptomatic and to describe the demographic characteristics and radiographic presentation of patients with bilateral OLT. To identify patients with bilateral OLT, we utilized a cross-sectional database of consecutive patients with a CT-proven OLT who had undergone bilateral CT scanning at our hospital between January 1989 and June 2021. The primary outcome was the prevalence of bilateral OLT. Patients with bilateral OLT were grouped into a unilaterally symptomatic group and a bilaterally symptomatic group. Patient and lesion characteristics were compared between these groups as well as between the symptomatic and asymptomatic ankles in the unilaterally symptomatic group. Radiographic examination included lesion volume, location, and morphology. Of 1,062 patients with OLT, 161 (15%) had bilateral OLT. Of the patients with bilateral OLT, 53 (33%) were bilaterally symptomatic. Patients who were bilaterally symptomatic were younger (p = 0.03) and more likely to present with a non-traumatic etiology (p < 0.01) in comparison with those who were unilaterally symptomatic. No differences were observed between the unilaterally and bilaterally symptomatic groups in terms of lesion morphology, volume, or location. In the unilaterally symptomatic group, lesion volume was significantly larger in symptomatic ankles in comparison with the contralateral, asymptomatic ankles (p < 0.01), but no significant differences were observed in terms of lesion morphology or location. In patients presenting with symptomatic OLT, the prevalence of bilateral OLT was 15%, and 1 in 3 patients with bilateral OLT were symptomatic on both sides. Larger lesion volume was associated with the presence of symptoms in patients with bilateral OLT. For patients with bilateral OLT, the treating team should be aware that younger patients and patients without a history of trauma are at a higher risk for having bilateral symptoms. Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Interleukin-10 deficiency aggravates traumatic brain injury in male but not female mice

The goal of this study was to determine whether deficiency of anti-inflammatory cytokine interleukin-10 (IL-10) affects traumatic brain injury (TBI) outcomes in a sex-dependent manner. Moderate TBI was induced by controlled cortical impact in 8-10 week-old wild-type and IL-10–deficient mice. In wild-type mice, serum IL-10 was significantly increased after TBI in males but not in females. At 4–5 weeks after TBI, sensorimotor function, cognitive function (Y-maze and novel object recognition tests), anxiety-related behavior (light-dark box and open field test), and depression-like behavior (forced swim test) were assessed. IL-10–deficient male mice had larger lesion volumes than did wild-type mice in the early recovery phase and worse performance on sensorimotor tasks, cognitive tests, and anxiety- and depression-related tests in the late recovery phase, whereas female IL-10–deficient mice had lesion volume equivalent to that of wild-type females and worse performance only on sensorimotor tasks. At 3 days after TBI, the number of GFAP- and Iba1-positive cells were augmented in areas in proximity to the injury (cerebral cortex and hippocampus) and in remote functional regions (striatum and amygdala) of IL-10–deficient male, but not female, mice. Moreover, on day 35, significantly fewer NeuN-positive cells were present in cortex, striatum, and amygdala of IL-10–deficient male mice than in wild-type males. This difference was not evident in females. We conclude that IL-10 deficiency aggravates cognitive and emotional recovery from TBI in association with enhanced gliosis and neuronal loss selectively in males, suggesting that recruitment of this cytokine limits damage in a sex-dependent manner.