Ipsilesional volume loss of basal ganglia and thalamus is associated with poor hand function after ischemic perinatal stroke

Background Perinatal stroke (PS) is the leading cause of hemiparetic cerebral palsy (CP). Involvement of the corticospinal tract on neonatal magnetic resonance imaging (MRI) is predictive of motor outcome in patients with hemiparetic CP. However, early MRI is not available in patients with delayed presentation of PS and prediction of hemiparesis severity remains a challenge. Aims To evaluate the volumes of the basal ganglia, amygdala, thalamus, and hippocampus following perinatal ischemic stroke in relation to hand motor function in children with a history of PS and to compare the volumes of subcortical structures in children with PS and in healthy controls. Methods Term born PS children with arterial ischemic stroke (AIS) (n = 16) and with periventricular venous infarction (PVI) (n = 18) were recruited from the Estonian Pediatric Stroke Database. MRI was accuired during childhood (4-18 years) and the volumes of the basal ganglia, thalamus, amygdala and hippocampus were calculated. The results of stroke patients were compared to the results of 42 age- and sex-matched healthy controls. Affected hand function was evaluated by Assisting Hand Assessment (AHA) and classified by the Manual Ability Classification System (MACS). Results Compared to the control group, children with AIS had smaller volumes of the ipsi- and contralesional thalami, ipsilesional globus pallidus, nucleus accumbens and hippocampus (p < 0.005). Affected hand function in children with AIS was correlated with smaller ipsilesional thalamus, putamen, globus pallidus, hippocampus, amygdala and contralesional amygdala (r > 0.5; p < 0.05) and larger volume of the contralesional putamen and hippocampus (r < − 0.5; p < 0.05). In children with PVI, size of the ipsilesional caudate nucleus, globus pallidus, thalamus (p ≤ 0.001) and hippocampus (p < 0.03) was smaller compared to controls. Smaller volume of the ipsi- and contralesional thalami and ipsilesional caudate nucleus was correlated with affected hand function (r > 0.55; p < 0.05) in children with PVI. Conclusions Smaller volume of ipsilesional thalamus was associated with poor affected hand function regardless of the perinatal stroke subtype. The pattern of correlation between hand function and volume differences in the other subcortical structures varied between children with PVI and AIS. Evaluation of subcortical structures is important in predicting motor outcome following perinatal stroke.

Predicting the Extent of Resection of Motor-Eloquent Gliomas Based on TMS-Guided Fiber Tracking

Background: Surgical planning with nTMS-based tractography is proven to increase safety during surgery. A preoperative risk stratification model has been published based on the M1 infiltration, RMT ratio, and tumor to corticospinal tract distance (TTD). The correlation of TTD with corticospinal tract to resection cavity distance (TRD) and outcome is needed to further evaluate the validity of the model. Aim of the study: To use the postop MRI-derived resection cavity to measure how closely the resection cavity approximated the preoperatively calculated corticospinal tract (CST) and how this correlates with the risk model and the outcome. Methods: We included 183 patients who underwent nTMS-based DTI and surgical resection for presumed motor-eloquent gliomas. TTD, TRD, and motor outcome were recorded and tested for correlations. The intraoperative monitoring documentation was available for a subgroup of 48 patients, whose responses were correlated to TTD and TRD. Results: As expected, TTD and TRD showed a good correlation (Spearman’s ρ = 0.67, p < 0.001). Both the TTD and the TRD correlated significantly with the motor outcome at three months (Kendall’s Tau-b 0.24 for TTD, 0.31 for TRD, p < 0.001). Interestingly, the TTD and TRD correlated only slightly with residual tumor volume, and only after correction for outliers related to termination of resection due to intraoperative monitoring events or the proximity of other eloquent structures (TTD ρ = 0.32, p < 0.001; TRD ρ = 0.19, p = 0.01). This reflects the fact that intraoperative monitoring (IOM) phenomena do not always correlate with preoperative structural analysis, and that additional factors influence the intraoperative decision to abort resection, such as the adjacency of other vulnerable structures. The TTD was also significantly correlated with variations in motor evoked potential (MEP) responses (no/reversible decrease vs. irreversible decrease; p = 0.03). Conclusions: The TTD approximates the TRD well, confirming the best predictive parameter and giving strength to the nTMS-based risk stratification model. Our analysis of TRD supports the use of the nTMS-based TTD measurement to estimate the resection preoperatively, also confirming the 8 mm cutoff. Nevertheless, the TRD proved to have a slightly stronger correlation with the outcome as the surgeon’s experience, anatomofunctional knowledge, and MEP observations influence the expected EOR.

Fast Outcome Categorization of the Upper Limb After Stroke

Background and Purpose: The ARAT (Action Research Arm Test) has been used to classify upper limb motor outcome after stroke in 1 of 3, 4, or 5 categories. The coronavirus disease 2019 (COVID-19) pandemic has encouraged the development of assessments that can be performed quickly and remotely. The aim of this study was to derive and internally validate decision trees for categorizing upper limb motor outcomes at the late subacute and chronic stages of stroke using a subset of ARAT tasks. Methods: This study retrospectively analyzed ARAT scores obtained in-person at 3 months poststroke from 333 patients. In-person ARAT scores were used to categorize patients’ 3-month upper limb outcome using classification systems with 3, 4, and 5 outcome categories. Individual task scores from in-person assessments were then used in classification and regression tree analyses to determine subsets of tasks that could accurately categorize upper limb outcome for each of the 3 classification systems. The decision trees developed using 3-month ARAT data were also applied to in-person ARAT data obtained from 157 patients at 6 months poststroke. Results: The classification and regression tree analyses produced decision trees requiring 2 to 4 ARAT tasks. The overall accuracy of the cross-validated decision trees ranged from 87.7% (SE, 1.0%) to 96.7% (SE, 2.0%). Accuracy was highest when classifying patients into one of 3 outcome categories and lowest for 5 categories. The decision trees are referred to as FOCUS (Fast Outcome Categorization of the Upper Limb After Stroke) assessments and they remained accurate for 6-month poststroke ARAT scores (overall accuracy range 83.4%–91.7%). Conclusions: A subset of ARAT tasks can accurately categorize upper limb motor outcomes after stroke. Future studies could investigate the feasibility and accuracy of categorizing outcomes using the FOCUS assessments remotely via video call.

Profile and early prediction of neuromotor outcome of very low birth weight infants

Background: Very low birth weight infants are at increased risk of developmental disorder. Early identification is necessary for planning and implementation of early intervention. Aims and Objective: To test the association of neurological examination at 40 weeks and 3 months with neuro motor outcome of VLBW infants at 24 months and to identify the perinatal and neonatal risk factors for atypical neurological outcome. Materials and Methods: It is a prospective cohort study. Consecutive 120 VLBW infants were enrolled in a single centre level III neonatal unit of a teaching hospital. Neuro motor assessment was done by Dubowitz neurological examination at 40 weeks and by Hammersmith infant neurological examination (HINE) at 3 months and 12 months at neurodevelopmental clinic. Motor assessment were performed by Alberta Infant Motor Scale (AIMS) at 6 and 12 months and by Bayley Scale of Infant & Toddler scale, (BSID) 3rd edition at 6,12 and 24 months respectively. All assessment ages were corrected for prematurity. Results: At 12 months 4.5% infants developed abnormal tone and 5.6% had motor delay. Four infants developed cerebral palsy at 24 months. Shock in neonatal period had significant association with suboptimal motor outcome at 12 months. Suboptimal HINE score at 12 months was rightly predicted at 3 months by HINE. Conclusion: Early anticipation and early identification of abnormal neuro motor outcome of VLBW infants can be used as simple and cost-effective measures for preventing long term neuro motor morbidity at resource limited countries.

Topographic Evolution of Anterior Cerebral Artery Infarction and Its Impact on Motor Impairment

<b><i>Introduction:</i></b> Motor deficit is common following anterior cerebral artery (ACA) stroke. This study aimed to determine the impact on the motor outcome, given the location of descending corticofugal fiber tracts (from the primary motor cortex [M1], dorsal and ventral premotor area [PMdv], and supplementary motor area [SMA]) and the regional variations in collateral support of the ACA territory. <b><i>Methods:</i></b> Patients with ACA vessel occlusion were included. Disruption to corticofugal fibers was inferred by overlap of tracts with a lesion on computed tomography perfusion at the onset and on magnetic resonance imaging (MRI) poststroke. The motor outcome was defined by dichotomized and combined National Institute of Health Stroke Scale (NIHSS) sub-scores for the arm and leg. Multivariate hierarchical partitioning was used to analyze the proportional contribution of the corticofugal fibers to the motor outcome. <b><i>Results:</i></b> Forty-seven patients with a median age of 77.5 (interquartile range 68.0–84.5) years were studied. At the stroke onset, 96% of patients showed evidence of motor deficit on the NIHSS, and the proportional contribution of the corticofugal fibers to motor deficit was M1-33%, SMA-33%, and PMdv-33%. By day 7, motor deficit was present in &#x3c;50% of patients and contribution of M1 fiber tracts to the motor deficit was reduced (M1-10.2%, SMA-61.0%, PMdv-28.8%). We confirmed our findings using publicly available high-resolution templates created from Human Connectome Project data. This also showed a reduction in involvement of M1 fiber tracts on initial perfusion imaging (33%) compared to MRI at a median time of 7 days poststroke (11%). <b><i>Conclusion:</i></b> Improvements in the motor outcome seen in ACA stroke may be due to the relative sparing of M1 fiber tracts from infarction. This may occur as a consequence of the posterior location of M1 fiber tracts and the evolving topography of ACA stroke due to the compensatory capacity of leptomeningeal anastomoses.

Technology-based therapy-response and prognostic biomarkers in a prospective study of a de novo Parkinson’s disease cohort

Early noninvasive reliable biomarkers are among the major unmet needs in Parkinson’s disease (PD) to monitor therapy response and disease progression. Objective measures of motor performances could allow phenotyping of subtle, undetectable, early stage motor impairments of PD patients. This work aims at identifying prognostic biomarkers in newly diagnosed PD patients and quantifying therapy-response. Forty de novo PD patients underwent clinical and technology-based kinematic assessments performing motor tasks (MDS-UPDRS part III) to assess tremor, bradykinesia, gait, and postural stability (T0). A visit after 6 months (T1) and a clinical and kinematic assessment after 12 months (T2) where scheduled. A clinical follow-up was provided between 30 and 36 months after the diagnosis (T3). We performed an ANOVA for repeated measures to compare patients’ kinematic features at baseline and at T2 to assess therapy response. Pearson correlation test was run between baseline kinematic features and UPDRS III score variation between T0 and T3, to select candidate kinematic prognostic biomarkers. A multiple linear regression model was created to predict the long-term motor outcome using T0 kinematic measures. All motor tasks significantly improved after the dopamine replacement therapy. A significant correlation was found between UPDRS scores variation and some baseline bradykinesia (toe tapping amplitude decrement, p = 0.009) and gait features (velocity of arms and legs, sit-to-stand time, p = 0.007; p = 0.009; p = 0.01, respectively). A linear regression model including four baseline kinematic features could significantly predict the motor outcome (p = 0.000214). Technology-based objective measures represent possible early and reproducible therapy-response and prognostic biomarkers.