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Objective Methods Results Interpretation Patient‐reported outcome measures (PROMs), which capture patients' perspectives on the consequences of health and disease, are widely used in neurological care and research. However, it is unclear how PROMs relate to performance‐rated impairments. Sociodemographic factors are known to affect PROMs. Direct damage to brain regions critical for self‐awareness (i.e., parietal regions and the salience/ventral‐attention network) may also impair self‐report outcomes. This study examined the relationship between PROMs and performance‐based measures in stroke survivors with arm motor impairments. We hypothesized that PROMs would be distinct from performance‐based outcomes, influenced by sociodemographic factors, and linked to damage in brain circuits involved in self‐perception.We longitudinally assessed 54 stroke survivors using patient‐reported and performance‐rated measures at 4 timepoints. We used factor analysis to reveal the outcome battery's factorial structure. Linear regression examined the association between classes of measures and sociodemographics. Voxel‐lesion‐symptom‐mapping, region‐of‐interest‐based analysis, and voxel‐lesion‐network‐mapping investigated the relationship between classes of outcomes and stroke‐related injury.Performance‐based and patient‐reported measures formed distinct factors, consistent across recovery phases. Higher education (β1 = 0.36, p = 0.02) and income adequacy (β2 = 0.48, p = 0.05) were associated with patient‐reported, but not performance‐rated outcomes. Greater parietal lobe injury, irrespective of hemisphere, was associated with worse patient‐reported outcomes; greater corticospinal tract injury related to worse performance‐rated outcomes. Lesions with greater functional connectivity to the salience/ventral‐attention network were associated with worse patient‐reported outcomes (r = −0.35, p = 0.009).Our findings reveal important differences between performance‐rated and patient‐reported outcomes, each with specific associated factors and anatomy post‐stroke. Incorporating sociodemographic and neuroanatomic characteristics into neurorehabilitation strategies may inform and optimize patient outcomes. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Background: Non-invasive brain mapping using navigated transcranial magnetic stimulation (nTMS) is a valuable tool prior to resection of malignant brain tumors. With nTMS motor mapping, it is additionally possible to analyze the function of the motor system and to evaluate tumor-induced neuroplasticity. Distinct changes in motor cortex excitability induced by certain malignant brain tumors are a focal point of research. Methods: A retrospective single-center study was conducted involving patients with malignant brain tumors. Clinical data, resting motor threshold (rMT), and nTMS-based tractography were evaluated. The interhemispheric rMT-ratio (rMTTumor/rMTControl) was calculated for each extremity and considered pathological if it was >110% or <90%. Distances between the corticospinal tract and the tumor (lesion-to-tract-distance -- LTD) were measured. Results: 49 patients were evaluated. 16 patients (32.7%) had a preoperative motor deficit. The cohort comprised 22 glioblastomas (44.9%), 5 gliomas of Classification of Tumors of the Central Nervous System (CNS WHO) grade 3 (10.2%), 6 gliomas of CNS WHO grade 2 (12.2%) and 16 cerebral metastases (32.7%). 26 (53.1%) had a pathological rMT-ratio for the upper extremity and 35 (71.4%) for the lower extremity. All patients with tumor-induced motor deficits had pathological interhemispheric rMT-ratios, and presence of tumor-induced motor deficits was associated with infiltration of the tumor to the nTMS-positive cortex (p = 0.04) and shorter LTDs (all p<0.021). Pathological interhemispheric rMT-ratio for the upper extremity was associated with cerebral metastases, but not with gliomas (p = 0.002). Conclusions: Our study underlines the diagnostic potential of nTMS motor mapping to go beyond surgical risk stratification. Pathological alterations in motor cortex excitability can be measured with nTMS mapping. Pathological cortical excitability was more frequent in cerebral metastases than in gliomas. [ABSTRACT FROM AUTHOR]

Introduction: Hypertensive intracerebral hemorrhage (HICH) is a condition associated with significant morbidity, mortality, and disability, particularly among the elderly population. The management of moderate thalamic-basal ganglia cerebral hemorrhage primarily relies on conservative approaches. Nevertheless, the rate of long-term disability remains high. In recent years, there has been significant advancement in minimally invasive surgery and diffusion tensor imaging techniques. Consequently, the utilization of Diffusion Tensor Imaging (DTI) technology in patients with cerebral haemorrhage allows for the identification of the haematoma's location in relation to the Corticospinal Tract (CST). This enables the development of precise puncture pathways that can be visualized, thereby avoiding any potential damage to the CST. Methods and analysis: Diffusion Tensor Imaging (DTI) is a method used to assess the structural and physiological characteristics of biological tissue by examining the diffusion behavior of water molecules.In the central nervous system, limb paralysis will be inevitable if the corticospinal tract is damaged. By employing DTI imaging techniques on individuals, it becomes possible to visualize the spatial relationship between the hematoma and the CST. This approach allows avoidance of the CST during preoperative planning of the puncture path, thus reducing secondary injuries caused by the procedure. The primary objective of this study was to assess the ability of patients in the minimally invasive surgery group and the conservative group to perform activities of daily living after 6 months of treatment. In addition, secondary outcomes included assessment of hematoma resorption/clearance ratios, cytokine levels, complication rates, and therapeutic indexes at different treatment durations, as well as long-term safety and efficacy at 2–3 years of follow-up. Furthermore, subgroup analysis, and sensitivity analysis were conducted to further analyze the data. Logistic single-variate and multivariate regression analyses were applied to understand the adverse factors affecting prognosis. Ethics and dissemination: The clinical study was reviewed and approved by the Ethics Committee of the First People's Hospital of Yibin. The ethical number is: 2023 Review (64). Registration number: This protocol is registered in the Prospective Registry of Chinese Clinical Trial Registries (PROCCTR). The full date of first registration is 28/12/2023. The registration number for PROCCTR is ChiCTR2300079252. [ABSTRACT FROM AUTHOR]

Background: Functional magnetic resonance imaging (fMRI) is widely used to depict neural activity and understand human brain function. Studies show that functional networks in gray matter undergo complex transformations from neonatal age to childhood, supporting rapid cognitive development. However, white matter functional networks, given the much weaker fMRI signal, have not been characterized until recently, and changes in white matter functional networks in the developing brain remain unclear. Purpose: Aims to examine and compare white matter functional networks in neonates and 8-year-old children. Methods: We acquired resting-state fMRI data on 69 full-term healthy neonates and 38 healthy 8-year-old children using a same imaging protocol and studied their brain white matter functional networks using a similar pipeline. First, we utilized the ICA method to extract white matter functional networks. Next, we analyzed the characteristics of the white matter functional networks from both time-domain and frequency-domain perspectives, specifically, intra-network functional connectivity (intra-network FC), inter-network functional connectivity (inter-network FC), and fractional amplitude of low-frequency fluctuation (fALFF). Finally, the differences in the above functional networks' characteristics between the two groups were evaluated. As a supplemental measure and to confirm with literature findings on gray matter functional network changes in the developing brain, we also studied and reported functional networks in gray matter. Results: White matter functional networks in the developing brain can be depicted for both the neonates and the 8-year-old children. White matter intra-network FC within the optic radiations, corticospinal tract, and anterior corona radiata was lower in 8-year-old children compared to neonates (p < 0.05). Inter-network FC between cerebral peduncle (CP) and anterior corona radiation (ACR) was higher in 8-year-olds (p < 0.05). Additionally, 8-year-olds showed a greater distribution of brain activity energy in the high-frequency range of 0.01–0.15 Hz. Significant developmental differences in brain white matter functional networks exist between the two group, characterized by increased inter-network FC, decreased intra-network FC, and higher high-frequency energy distribution. Similar findings were also observed in gray matter functional networks. Conclusion: White matter functional networks can be reliably measured in the developing brain, and the differences in these networks reflect functional differentiation and integration in brain development. [ABSTRACT FROM AUTHOR]

Disruptions in the brain's connections to the hands resulting from a cervical spinal cord injury (cSCI) can lead to severe and persistent functional impairments. The integrity of these connections is an important predictor of upper extremity recovery in stroke and may similarly act as a biomarker in cSCI. In this perspective article, we review recent findings from a large cohort of individuals with cSCI, demonstrating the predictive value of corticospinal tract (CST) integrity in cSCI—CST sparing. This research underscores that, akin to stroke, the integrity of brain-to-hand connections is crucial for predicting upper extremity recovery following cSCI. We address the limitations of commonly used metrics, such as sacral sparing and the concept of central cord syndrome. Furthermore, we offer insights on emerging metrics, such as tissue bridges, emphasizing their potential in assessing the integrity of brain connections to the spinal cord. [ABSTRACT FROM AUTHOR]

Motor-evoked potential (MEP) monitoring by transcranial electrical stimulation (TES) is important for intraoperative motor function assessment in neurosurgery; however, false-negative results sometimes occur, and these findings should be interpreted with caution. Herein, we report an interesting MEP change resulting from a pons transection. The patient was a boy aged 5 years and 2 months. He underwent multiple craniotomies for cerebellar anaplastic ependymoma and was already paralyzed in the right upper and lower limbs. Therefore, we decided to remove the recurrent lesion from the left anterior pons. MEPs were recorded on both the right and left sides after the start of surgery but disappeared 1 h 30 min after the start of surgery in the TES on the operative side, even when the stimulation intensity was increased. The contralateral TES consistently recorded stable MEPs throughout the surgery. The tumor was completely resected on imaging. Immediately postoperatively, the patient experienced flaccid paralysis on the right side of the body, which recovered to preoperative levels over time. A transcranial MEP cannot be derived if the corticospinal tract is transected at the pons. Transcranial MEP findings may accurately reflect the corticospinal tract function if the injury is caudal to the pons. [ABSTRACT FROM AUTHOR]

Objectives: To assess the feasibility, characteristics and prognostic value of prenatal visualization of the corticospinal tracts (CSTs) using diffusion‐weighted magnetic resonance imaging (MRI)‐based tractography in fetuses with intraventricular hemorrhage (IVH). Methods: This was a retrospective single‐center cohort study of singleton fetuses diagnosed with IVH on MRI from January 2011 to December 2018. The left and right CSTs were reconstructed according to an in‐utero diffusion tensor imaging sequence using a multi‐region of interest (ROI) deterministic tractography approach. The CSTs were segmented by two polygonal ROI: at the level of the posterior limb of the internal capsule and the crus cerebri. The morphology and integrity of the CSTs were assessed visually. Internal capsule and crus cerebri apparent diffusion coefficient and fractional anisotropy values were measured. Postnatal motor function data were obtained from the parents using the functional status scale. Results: A total of 35 fetuses with IVH (mean ± SD gestational age, 29.1 ± 5.1 (range, 19.9–38.9) weeks) were included in the analysis. Parenchymal involvement on T2‐weighted sequences was demonstrated in 19 (54%) of the cohort. CST involvement correlated significantly with the presence of parenchymal damage on T2‐weighted imaging (P = 0.02). Among liveborn cases, the rate of motor impairment was 14% (1/7) in children with intact CSTs compared with 100% (5/5) in cases in which the CSTs were impaired (P = 0.015). Conclusions: Fetal corticospinal tractography is feasible technically and offers valuable prognostic information. It enhances parental counseling by providing insights into potential motor outcome, underscoring its utility in complementing fetal neurosonography in cases of prenatal IVH. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Chronic pain is common in young people and can have a major life impact. Despite the burden of chronic pain, mechanisms underlying chronic pain development and persistence are still poorly understood. Specifically, white matter (WM) connectivity has remained largely unexplored in pediatric chronic pain. Using diffusion-weighted imaging, this study examined WM microstructure in adolescents (age M 5 15.8 years, SD 5 2.8 years) with chronic pain (n 5 44) compared with healthy controls (n 5 24). Neurite orientation dispersion and density imaging modeling was applied, and voxel-based whole-white-matter analyses were used to obtain an overview of potential alterations in youth with chronic pain and tract-specific profile analyses to evaluate microstructural profiles of tracts of interest more closely. Our main findings are that (1) youth with chronic pain showed widespread elevated orientation dispersion compared with controls in several tracts, indicative of less coherence; (2) signs of neurite density tract-profile alterations were observed in several tracts of interest, with mainly higher density levels in patients; and (3) several WM microstructural alterations were associated with pain catastrophizing in the patient group. Implicated tracts include both those connecting cortical and limbic structures (uncinate fasciculus, cingulum, anterior thalamic radiation), which were associated with pain catastrophizing, as well as sensorimotor tracts (corticospinal tract). By identifying alterations in the biologically informative WM microstructural metrics orientation dispersion and neurite density, our findings provide important and novel mechanistic insights for understanding the pathophysiology underlying chronic pain. Taken together, the data support alterations in fiber organization as a meaningful characteristic, contributing process to the chronic pain state. [ABSTRACT FROM AUTHOR]

Purpose: To compare MR axon radius estimation in human white matter using a multiband spiral sequence combined with field monitoring to the current state‐of‐the‐art echo‐planar imaging (EPI)‐based approach. Methods: A custom multiband spiral sequence was used for diffusion‐weighted imaging at ultra‐high b$$ b $$‐values. Field monitoring and higher order image reconstruction were employed to greatly reduce artifacts in spiral images. Diffusion weighting parameters were chosen to match a state‐of‐the art EPI‐based axon radius mapping protocol. The spiral approach was compared to the EPI approach by comparing the image signal‐to‐noise ratio (SNR) and performing a test–retest study to assess the respective variability and repeatability of axon radius mapping. Effective axon radius estimates were compared over white matter voxels and along the left corticospinal tract. Results: Increased SNR and reduced artifacts in spiral images led to reduced variability in resulting axon radius maps, especially in low‐SNR regions. Test–retest variability was reduced by a factor of approximately 1.5 using the spiral approach. Reduced repeatability due to significant bias was found for some subjects in both spiral and EPI approaches, and attributed to scanner instability, pointing to a previously unknown limitation of the state‐of‐the‐art approach. Conclusion: Combining spiral readouts with field monitoring improved mapping of the effective axon radius compared to the conventional EPI approach. [ABSTRACT FROM AUTHOR]

Injuries to the central nervous system (CNS) can cause severe neurological deficits. Axonal regrowth is a fundamental process for the reconstruction of compensatory neuronal networks after injury; however, it is extremely limited in the adult mammalian CNS. In this study, we conducted a loss-of-function genetic screen in cortical neurons, combined with a Web resource-based phenotypic screen, and identified synaptotagmin 4 (Syt4) as a novel regulator of axon elongation. Silencing Syt4 in primary cultured cortical neurons inhibits neurite elongation, with changes in gene expression involved in signaling pathways related to neuronal development. In a spinal cord injury model, inhibition of Syt4 expression in cortical neurons prevented axonal sprouting of the corticospinal tract, as well as neurological recovery after injury. These results provide a novel therapeutic approach to CNS injury by modulating Syt4 function. [ABSTRACT FROM AUTHOR]

Diffusion-weighted magnetic resonance imaging (DMRI) is a potential tool to assess changes in brain connectivity and microstructure resulting from physical and occupational therapy in young children with cerebral palsy. This works was carried out to assess whether DMRI can detect changes after 36 weeks of physical and occupational therapy in the microstructure and connectivity of the brains of children with cerebral palsy and determine whether imaging findings correlate with changes in clinical measures of motor function. Five children underwent anatomical MRI and DMRI and evaluations of motor function skills at baseline and after 36 weeks of intensive or once-weekly physical and occupational Perception-Action Approach therapies. Diffusion tensor imaging and constrained spherical deconvolution methods were used to calculate fractional anisotropy (FA) and fiber orientation distribution functions (fODFs), respectively. The fODFs were used to generate tractograms of the cerebrospinal tract (CST). After 36 weeks of physical and occupational therapy, all children showed increases in motor function. No changes were observed in anatomical MRI before and after therapy but CST tractography did show small differences indicating possible altered microstructure and connectivity in the brain. FA values along the CSTs, however, showed no significant changes. Reliable longitudinal DMRI can be employed in toddler-aged children with CP and DMRI has the potential to monitor neuroplastic changes in white matter microstructure. However, there is a high variability between subjects and clinical improvements were not always correlated with measures of FA along the CST. [ABSTRACT FROM AUTHOR]

Long-range axonal projections of diverse classes of neocortical excitatory neurons likely contribute to brain-wide interactions processing sensory, cognitive and motor signals. Here, we performed light-sheet imaging of fluorescently labeled axons from genetically defined neurons located in posterior primary somatosensory barrel cortex and supplemental somatosensory cortex. We used convolutional networks to segment axon-containing voxels and quantified their distribution within the Allen Mouse Brain Atlas Common Coordinate Framework. Axonal density was analyzed for different classes of glutamatergic neurons using transgenic mouse lines selectively expressing Cre recombinase in layer 2/3 intratelencephalic projection neurons (Rasgrf2-dCre), layer 4 intratelencephalic projection neurons (Scnn1a-Cre), layer 5 intratelencephalic projection neurons (Tlx3-Cre), layer 5 pyramidal tract projection neurons (Sim1-Cre), layer 5 projection neurons (Rbp4-Cre), and layer 6 corticothalamic neurons (Ntsr1-Cre). We found distinct axonal projections from the different neuronal classes to many downstream brain areas, which were largely similar for primary and supplementary somatosensory cortices. Functional connectivity maps obtained from optogenetic activation of sensory cortex and wide-field imaging revealed topographically organized evoked activity in frontal cortex with neurons located more laterally in somatosensory cortex signaling to more anteriorly located regions in motor cortex, consistent with the anatomical projections. The current methodology therefore appears to quantify brain-wide axonal innervation patterns supporting brain-wide signaling. [ABSTRACT FROM AUTHOR]

This study develops explainable artificial intelligence for predicting safe balance using hospital data, including clinical, neurophysiological, and diffusion tensor imaging properties. Retrospective data from 92 first-time stroke patients from January 2016 to June 2023 was analysed. The dependent variables were independent mobility scores, i.e., Berg Balance Scales with 0 (45 or below) vs. 1 (above 45) measured after three and six months, respectively. Twenty-nine predictors were included. Random forest variable importance was employed for identifying significant predictors of the Berg Balance Scale and testing its associations with the predictors, including Berg Balance Scale after one month and corticospinal tract diffusion tensor imaging properties. Shapley Additive Explanation values were calculated to analyse the directions of these associations. The random forest registered a higher or similar area under the curve compared to logistic regression, i.e., 91% vs. 87% (Berg Balance Scale after three months), 92% vs. 92% (Berg Balance Scale after six months). Based on random forest variable importance values and rankings: (1) Berg Balance Scale after three months has strong associations with Berg Balance Scale after one month, Fugl-Meyer assessment scale, ipsilesional corticospinal tract fractional anisotropy, fractional anisotropy laterality index and age; (2) Berg Balance Scale after six months has strong relationships with Fugl-Meyer assessment scale, Berg Balance Scale after one month, ankle plantar flexion muscle strength, knee extension muscle strength and hip flexion muscle strength. These associations were positive in the SHAP summary plots. Including Berg Balance Scale after one month, Fugl-Meyer assessment scale or ipsilesional corticospinal tract fractional anisotropy in the random forest will increase the probability of Berg Balance Scale after three months being above 45 by 0.11, 0.08, or 0.08. In conclusion, safe balance after stroke strongly correlates with its initial motor function, Fugl-Meyer assessment scale, and ipsilesional corticospinal tract fractional anisotropy. Diffusion tensor imaging information aids in developing explainable artificial intelligence for predicting safe balance after stroke. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation After severe corticospinal tract damage poststroke in humans, some recovery of strength and movement proximally is evident. It is possible that alternate motor pathways, such as the reticulospinal tract, may be upregulated to compensate for the loss of corticospinal tract input. We investigated the extent of reticulospinal tract excitability modulation and its inter‐dependence on the severity of corticospinal tract damage after stroke in humans.We used a novel startle conditioned transcranial magnetic stimulation paradigm to elicit ipsilateral motor evoked potentials, an index of reticulospinal tract excitability, in 22 chronic stroke participants with mild to severe corticospinal tract damage and 14 neurotypical age‐matched controls.We found that ipsilateral motor evoked potential presence was higher in the paretic arm of people with severe corticospinal tract damage compared to their non‐paretic arm, people with mild corticospinal tract damage, and age‐matched controls. Interestingly, ipsilateral motor evoked potential presence was correlated with motor impairment across the entire stroke cohort, whereby individuals with worse impairment exhibited more frequent ipsilateral motor evoked potentials (ie, higher reticulospinal tract excitability).Following severe corticospinal tract damage, upregulated reticulospinal tract activity may compensate for a loss of corticospinal tract input, providing some proximal recovery of isolated and within‐synergy movements, but deficits in performing out of synergy movements and finger fractionation remain. Interventions aimed at modulating the reticulospinal tract could be beneficial or detrimental to ameliorating motor impairment depending on the degree of reliance on this pathway for residual motor output. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Objectives: Neuroimaging studies of dyskinetic cerebral palsy (CP) are scarce and the neuropathological underpinnings are not fully understood. We delineated the corticospinal tract (CST) and cortico‐striatal‐thalamocortical (CSTC) pathways with probabilistic tractography to assess their (1) integrity and (2) association with motor functioning in people with dyskinetic CP. Methods: Diffusion weighted magnetic resonance images were obtained for 33 individuals with dyskinetic CP and 33 controls. Fractional anisotropy (FA) and mean diffusivity (MD) for the CST and the CSTC pathways were compared between groups. Correlation analyses were performed between tensor metric values and motor function scores of participants with dyskinetic CP as assessed by the Gross Motor Function Classification System (GMFCS), the Bimanual Fine Motor Function (BFMF), and the Manual Ability Classification System (MACS). Results: White matter integrity in both the CST and the CSTC pathways was reduced in people with dyskinetic CP. The GMFCS, MACS and, less commonly, the BFMF were associated with FA and, particularly, MD in most portions of these pathways. Interpretation: The present study advances our understanding of the involvement of white matter microstructure in sensorimotor pathways and its relationship with motor impairment in people with dyskinetic CP. Our results are consistent with well‐described relationships between upper limb function and white matter integrity in the CST and CSTC pathways in other forms of CP. This knowledge may ultimately help prognosis and therapeutic programmes. [ABSTRACT FROM AUTHOR]

Objective: This study aims to assess the microstructural abnormalities in white matter (WM) among Behcet's disease (BD) patients, both with and without neurological involvement, utilising tract-based spatial statistics (TBSS) to elucidate the underlying causes of WM microstructural changes. Methods: This prospective study comprised 43 BD patients without neurological involvement, 15 neuro-Behcet's disease (NBD) patients with normal conventional MRI, and 54 healthy controls matched for age and sex. TBSS was applied in this diffusion tensor imaging study to conduct a whole-brain voxel-wise analysis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of WM. Results: Compared to the control group, BD patients exhibited decreased FA and increased MD and RD in nearly all WM tracts, along with increased AD in the left corticospinal tract (CST), left inferior longitudinal fasciculus (ILF), and left superior longitudinal fasciculus (SLF). NBD patients also showed a widespread decrease in FA and increased MD and RD, similar to BD patients without neurological involvement. Additionally, NBD patients had increased AD in the left CST, left ILF, left SLF, left inferior fronto-occipital fasciculus (IFOF), and right CST. Compared to BD patients without neurological involvement, NBD patients exhibited a greater reduction in FA and an increase in MD and RD in WM tracts, with no significant differences in AD. Conclusion: These results suggest that the main mechanism of microstructural changes in the WM of BD patients may be related to impaired fibre integrity, demyelination, and decreased myelin sheath integrity. Advances in knowledge: This study demonstrated BD patients without neurological involvement and NBD patients a decrease in FA and an increase in MD and RD were observed in larger areas of major WM tracts, while an increase in AD values was observed in fewer tracts. Our findings may be useful in understanding the pathophysiology underlying subclinical parenchymal involvement and neurological dysfunction in BD patients and the management of BD patients. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a 23-year-old male with juvenile parkinsonism and cognitive impairment due to compound heterozygous variants in the BTD gene, leading to biotinidase deficiency. The patient showed symptoms of stiffness, tremors, delayed development milestones, and cognitive impairments. Treatment with biotin supplementation and dopaminergic therapy showed improvement in motor symptoms but not in cognitive functions. The study highlights the importance of considering biotinidase deficiency in cases of juvenile parkinsonism, especially when accompanied by developmental delays, cognitive impairments, and specific MRI findings. [Extracted from the article]

Hereditary spastic paraplegias are rare genetic disorders characterized by corticospinal tract impairment. Spastic paraplegia 83 (SPG83) is associated with biallelic mutations in the HPDL gene, leading to varied severities from neonatal to juvenile onset. The function of HPDL is unclear, though it is speculated to play a role in alternative coenzyme Q10 biosynthesis. Here, we report the generation of hiPS lines from primary skin fibroblasts derived from three SPG83 patients with different HPDL mutations, using episomal reprogramming. The patients' clinical characteristics are carefully listed. The hiPS lines were meticulously characterized, demonstrating typical pluripotent characteristics through immunofluorescence assays for stemness markers (OCT4, TRA1-60, NANOG, and SSEA4) and RT-PCR for endogenous gene expression. Genetic integrity and identity were confirmed via Sanger sequencing and short tandem repeat analysis. These hiPS cells displayed typical pluripotent characteristics and were able to differentiate into neocortical neurons via a dual SMAD inhibition protocol. In addition, HPDL mutant neurons assessed via long-term culturing were able to achieve effective maturation, similarly to their wild-type counterparts. The HPDL hiPS lines we generated will provide a valuable model for studying SPG83, offering insights into its molecular mechanisms and potential for developing targeted therapies. [ABSTRACT FROM AUTHOR]

Subtle motor signs are a common feature in children with attention‐deficit/hyperactivity disorder (ADHD). It has long been suggested that white matter abnormalities may be involved in their presentation, though no study has directly probed this question. The aim of this study was to investigate the relationship between white matter organization and the severity of subtle motor signs in children with and without ADHD. Participants were 92 children with ADHD aged between 8 and 12 years, and 185 typically developing controls. Subtle motor signs were examined using the Physical and Neurological Examination for Soft Signs (PANESS). Children completed diffusion MRI, and fixel‐based analysis was performed after preprocessing. Tracts of interest were delineated using TractSeg including the corpus callosum (CC), the bilateral corticospinal tracts (CST), superior longitudinal fasciculus, and fronto‐pontine tracts (FPT). Fiber cross‐section (FC) was calculated for each tract. Across all participants, lower FC in the CST was associated with higher PANESS Total score (greater motor deficits). Within the PANESS, similar effects were observed for Timed Left and Right maneuvers of the hands and feet, with lower FC of the CST, CC, and FPT associated with poorer performance. No significant group differences were observed in FC in white matter regions associated with PANESS performance. Our data are consistent with theoretical accounts implicating white matter organization in the expression of motor signs in childhood. However, rather than contributing uniquely to the increased severity of soft motor signs in those with ADHD, white matter appears to contribute to these symptoms in childhood in general. [ABSTRACT FROM AUTHOR]

Cerebral adrenoleukodystrophy (CALD) is an X-linked rapidly progressive demyelinating disease leading to death usually within a few years. The standard of care is haematopoietic stem cell transplantation (HSCT), but many men are not eligible due to age, absence of a matched donor or lesions of the corticospinal tracts (CST). Based on the ADVANCE study showing that leriglitazone decreases the occurrence of CALD, we treated 13 adult CALD patients (19–67 years of age) either not eligible for HSCT (n = 8) or awaiting HSCT (n = 5). Patients were monitored every 3 months with standardized neurological scores, plasma biomarkers and brain MRI comprising lesion volumetrics and diffusion tensor imaging. The disease stabilized clinically and radiologically in 10 patients with up to 2 years of follow-up. Five patients presented with gadolinium enhancing CST lesions that all turned gadolinium negative and, remarkably, regressed in four patients. Plasma neurofilament light chain levels stabilized in all 10 patients and correlated with lesion load. The two patients who continued to deteriorate were over 60 years of age with prominent cognitive impairment. One patient died rapidly from coronavirus disease 2019. These results suggest that leriglitazone can arrest disease progression in adults with early-stage CALD and may be an alternative treatment to HSCT. [ABSTRACT FROM AUTHOR]

Introduction: LMNB1-related autosomal dominant leukodystrophy (ADLD) is a slowly progressive neurodegenerative disorder caused by overexpression of LMNB1. We retrospectively reviewed charts of all ADLD patients seen at Mayo Clinic. Methods: All available data from molecularly confirmed ADLD patients was reviewed. Results: Of eight patients identified, three were male. Age at symptom onset ranged from 33 to 64 years. In males, the first symptom was erectile dysfunction (2/3) or neurogenic bladder (1/3) and, in females, weakness (3/5), bladder dysfunction (2/5), or depression (1/5). Diagnostic delay from symptom onset was a median of 6 (IQR 2.3–10) years. Other reported symptoms included cognitive difficulties (8/8), fatigue (7/8), sleep issues (4/8), mood disturbances (5/8), tremor (4/8), and migraine (4/8). Family history was positive in 6. All eight patients had LMNB1 duplication. Eighteen brain MRIs were reviewed from 7 patients. All showed symmetric confluent T2W deep cerebral and periventricular white matter hyperintensities with involvement of the posterior limb of the internal capsule, corpus callosum, corticospinal tract in brain stem, and superior and middle cerebellar peduncles. Seven spine MRIs from six patients showed moderate diffuse atrophy of the spinal cord. Conclusion: Typical clinical symptoms and characteristic MRI changes should prompt genetic testing for ADLD. [ABSTRACT FROM AUTHOR]

Plantarflexors provide propulsion during walking and receive input from both corticospinal and corticoreticulospinal tracts, which exhibit some frequency-specificity that allows potential differentiation of each tract's descending drive. Given that stroke may differentially affect each tract and impair the function of plantarflexors during walking; here, we examined this frequency-specificity and its relation to walking-specific measures during post-stroke walking. Fourteen individuals with chronic stroke walked on an instrumented treadmill at self-selected and fast walking speed (SSWS and FWS, respectively) while surface electromyography (sEMG) from soleus (SOL), lateral gastrocnemius (LG), and medial gastrocnemius (MG) and ground reaction forces (GRF) were collected. We calculated the intermuscular coherences (IMC; alpha, beta, and low-gamma bands between SOL–LG, SOL–MG, LG–MG) and propulsive impulse using sEMG and GRF, respectively. We examined the interlimb and intralimb IMC comparisons and their relationships with propulsive impulse and walking speed. Interlimb IMC comparisons revealed that beta LG–MG (SSWS) and low-gamma SOL–LG (FWS) IMCs were degraded on the paretic side. Intralimb IMC comparisons revealed that only alpha IMCs (both speeds) exhibited a statistically significant difference to random coherence. Further, alpha LG–MG IMC was positively correlated with propulsive impulse in the paretic limb (SSWS). Alpha and beta/low-gamma bands may have a differential functional role, which may be related to the frequency-specificity of the underlying descending drives. The persistence of alpha band in plantarflexors and its strong positive relationship with propulsive impulse suggests relative alteration of corticoreticulospinal tract after stroke. These findings imply the presence of frequency-specific descending drives to walking-specific muscles in chronic stroke. [ABSTRACT FROM AUTHOR]

[Display omitted] • Spinal cord injury damages axons, causing loss of motor and sensory function. • Promoting and guiding axonal regrowth is essential for functional recovery. • 3D-printed, electroconductive scaffolds with tuneable geometries were developed. • Scaffolds were functionalised with aligned, neurotrophic extracellular matrix. • Electrostimulation via scaffolds significantly increased outgrowth from neurons. Spinal cord injury (SCI) is a devastating neurotrauma, affecting 250,000 to 500,000 people annually, and typically results in paralysis. Electrostimulation can promote neuronal growth, but the formation of a lesion cavity post-SCI inhibits regrowth, limiting its efficacy. Bridging the lesion with a structured, electroactive substrate to direct electrostimulation to growing neurites could support and drive neuronal regrowth through the lesion to enable functional recovery but to date, no such platform exists. This study describes the development of an electroconductive (15 ± 5 S/m), 3D-printed scaffold, comprising a polypyrrole/polycaprolactone framework filled with biomimetic & neurotrophic extracellular matrix. 3D printing allowed inclusion of channels in the scaffold designed to mimic the size of human corticospinal tracts to direct electrostimulation to growing neurons. Scaffolds exhibited excellent biocompatibility with both neurons and human primary astrocytes and maintained electrical and biofunctionality when scaled to match the size of human corticospinal tracts. When neurons were cultured for 7 days on the scaffolds under continuous electrostimulation (200 mV/mm, 12 Hz), significantly longer neurites were observed on electrically stimulated electroconductive scaffolds. These results demonstrate that electrostimulation applied via an anatomically-mimetic, 3D-printed electroconductive scaffold drives neurite outgrowth and represents a promising approach for treatment of spinal cord injury. [ABSTRACT FROM AUTHOR]

Resection of a glioma from the dorsomedial frontal lobe, including the supplementary motor area (SMA), can result in postoperative SMA syndrome. SMA syndrome may occur during awake craniotomies. However, it is often difficult to intraoperatively distinguish between motor dysfunction due to pyramidal tract damage from that due to SMA syndrome. Patients with suspected intraoperative SMA syndrome are indifferent to their surroundings, have stiff facial muscles, and maintain a fixed gaze. We defined this condition as "apathetic look." The present study aimed to investigate whether intraoperative "apathetic look" is useful for identifying intraoperative SMA syndrome in patients with glioma close to motor-related areas, including the SMA, during awake craniotomy. This study included 33 consecutive patients with glioma included in the SMA. We excluded patients whose tumors extended to motor-related areas. We also assessed whether intraoperative SMA syndrome occurred in each patient. We evaluated the correlation between the occurrence of intraoperative SMA syndrome and various clinical factors, including intraoperative "apathetic look." Of the 33 patients, 12 had intraoperative SMA syndrome. Intraoperative "apathetic look" showed strong correlation with intraoperative SMA syndrome (p < 0.0001). Additionally, higher extent of resection (EOR) and resection of the corpus callosum showed a significantly higher incidence of intraoperative "apathetic look." All 12 patients with intraoperative SMA syndrome showed intraoperative "apathetic look" and recovered from SMA syndrome with high EOR. In conclusion, intraoperative "apathetic look" shows strong correlation with intraoperative SMA syndrome. Therefore, "apathetic look" may be a valuable indicator of intraoperative SMA syndrome during awake craniotomy. [ABSTRACT FROM AUTHOR]

Upper limb actions require intersegmental coordination of the scapula, shoulders, elbows, forearms, wrists, and hand muscles. Stroke hemiparesis, presenting as an impairment of an intersegmentally coordinated voluntary movement, is associated with altered integrity of corticospinal tract (CST) transmission from the motor cortex (M1) to muscles. Motor evoked potentials (MEPs) elicited by M1 transcranial magnetic stimulation (TMS) of "at rest" muscles, or as a backup, during muscle contraction have been used to identify CST integrity and predict the outcome after hemiparesis, under the implicit assumption that MEPs present in only one or two muscles are manifest surrogates of CST integrity for other muscles of the upper limbs. This study presents a method for applying TMS during motor tasks that involve proximal and distal muscles. It focuses on evaluating multi-muscle electromyography (EMG) and MEPs across all task-relevant limb segments. Protocols are presented for assessing voluntary motor behavior in individuals with hemiparetic stroke using isometric, unimanual, bimanual, and "REST" conditions that broaden the concept of the degree of CST integrity in order to inform clinical prescription for neurorehabilitation and distinguish its potential as a prognostic tool. Data describing the recordings of multi-muscle transcranial magnetic stimulation induced motor evoked potentials (TMS-MEP) will be presented in a case of subacute hemiparetic stroke to elucidate our perspective. [ABSTRACT FROM AUTHOR]

Background. Dry needling (DN) is a technique employed to mitigate spasticity and enhance functionality in stroke patients. We report the impact of DN on both corticospinal tract (CST) consistency and wrist flexors spasticity of an individual affected by stroke. Case. The participant was a 57‐year‐old male who had experienced an ischemic stroke 9 months prior. The primary outcome measures included fractional anisotropy (FA), asymmetry FA (aFA), ratio FA (rFA), and Modified Modified Ashworth Scale (MMAS). Additionally, secondary outcomes encompassed wrist extension range of motion (ROM) and performance in the box and block test (BBT). These measurements were taken both before and after the administration of DN treatment. Results. After the application of DN, the mean FA of the ipsilesional CST increased from 0.35 to 0.39, concomitantly with a decline in aFA from 0.18 to 0.13. Notably, the rFA exhibited a pre‐DN value of 0.69, which subsequently rose to 0.76 post‐DN. Moreover, a significant reduction in MMAS scores was detected, from a score of "3" prior to DN application to a post‐DN score of "1". In terms of wrist mobility, both active and passive extension ROM exhibited favorable improvements, with an increase of 12° for active extension and 16° for passive extension. Furthermore, there was a substantial improvement in the BBT score, an indicator of manual dexterity, ascending from 12 to 24. Conclusion. Enhancements in CST consistency suggest it as a potential mechanism contributing to the observed improvements following DN in this stroke case. [ABSTRACT FROM AUTHOR]

Objective: The corticospinal tract (CST) is considered the most important motor output pathway comprising fibers from the primary motor cortex (M1) and various premotor areas. Damage to its descending fibers after stroke commonly leads to motor impairment. While premotor areas are thought to critically support motor recovery after stroke, the functional role of their corticospinal output for different aspects of post‐stroke motor control remains poorly understood. Methods: We assessed the differential role of CST fibers originating from premotor areas and M1 in the control of basal (single‐joint muscle synergies and strength) and complex motor control (involving inter‐joint coordination and visuomotor integration) using a novel diffusion imaging approach in chronic stroke patients. Results: While M1 sub‐tract anisotropy was positively correlated with basal and complex motor skills, anisotropy of PMd, PMv, and SMA sub‐tracts was exclusively associated with complex motor tasks. Interestingly, patients featuring persistent motor deficits showed an additional positive association between premotor sub‐tract integrity and basal motor control. Interpretation: While descending M1 output seems to be a prerequisite for any form of upper limb movements, complex motor skills critically depend on output from premotor areas after stroke. The additional involvement of premotor tracts in basal motor control in patients with persistent deficits emphasizes their compensatory capacity in post‐stroke motor control. In summary, our findings highlight the pivotal role of descending corticospinal output from premotor areas for motor control after stroke, which thus serve as prime candidates for future interventions to amplify motor recovery. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the relationship between sleep stages and neural microstructure – measured using diffusion tensor imaging – of the posterior limb of the internal capsule and corticospinal tract in preterm infants. A retrospective cohort of 50 preterm infants born between 24 + 4 and 29 + 3 weeks gestational age was included in the study. Sleep stages were continuously measured for 5–7 consecutive days between 29 + 0 and 31 + 6 weeks postmenstrual age using an in-house-developed, and recently published, automated sleep staging algorithm based on routinely measured heart rate and respiratory rate. Additionally, a diffusion tensor imaging scan was conducted at term equivalent age as part of standard care. Region of interest analysis of the posterior limb of the internal capsule was performed, and tractography was used to analyze the corticospinal tract. The association between sleep and white matter microstructure of the posterior limb of the internal capsule and corticospinal tract was examined using a multiple linear regression model, adjusted for potential confounders. The results of the analyses revealed an interaction effect between sleep stage and days of invasive ventilation on the fractional anisotropy of the left and right posterior limb of the internal capsule (β = 0.04, FDR-adjusted p = 0.001 and β = 0.04, FDR-adjusted p = 0.02, respectively). Furthermore, an interaction effect between sleep stage and days of invasive ventilation was observed for the radial diffusivity of the mean of the left and right PLIC (β = −4.1e-05, FDR-adjusted p = 0.04). Previous research has shown that, in very preterm infants, invasive ventilation has a negative effect on white matter tract maturation throughout the brain. A positive association between active sleep and white matter microstructure of the posterior limb of the internal capsule, may indicate a protective role of sleep in this vulnerable population. • Active sleep positively influences white matter microstructure in preterm infants. • Interaction between sleep stages and days of invasive ventilation affects brain development. • Active sleep shows a protective role in preterm infants with longer invasive ventilation days. • Increased AS is associated with higher fractional anisotropy in the PLIC. [ABSTRACT FROM AUTHOR]

Hashimoto's encephalopathy is an autoimmune disease characterized by diverse clinical and imaging manifestations, often presenting considerable challenges in its diagnosis, especially when myelitis occurs before the onset of encephalopathy. Anti-N-terminal of α-enolase antibodies targeting the N-terminal of α-enolase are specific serum markers of Hashimoto's encephalopathy; however, studies analyzing their association with myelitis are lacking. Herein, we describe the case of a patient with myelitis who later developed encephalopathy. Owing to positivity for anti-N-terminal of α-enolase antibodies in the serum, a diagnosis of Hashimoto's encephalopathy was made. Detecting anti-NAE antibodies can be useful in diagnosing myelitis of unknown etiology.

Background and Purpose: The role of asymptomatic diffusion‐weighted imaging‐positive (aDWI+) lesions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients remains unclear, and their radiographic features may differ from those of symptomatic diffusion‐weighted imaging‐positive (sDWI+) lesions. We aimed to investigate the clinicoradiographic characteristics of aDWI+ lesions in CADASIL patients. Methods: We conducted a retrospective analysis using data from the Taiwan CADASIL Registry. aDWI+ lesions were defined as incidentally detected DWI+ lesions without corresponding acute neurological deficits. We compared the baseline clinical characteristics of patients with and without aDWI+ lesions and analyzed their radiological features and evolution in relation to sDWI+ lesions. Results: Among 154 enrolled patients (mean age 62 ± 10 years), 17 (11%) had aDWI+ lesions. Baseline clinical characteristics were similar in the two groups, but those with aDWI+ lesions had more lacunes (median 8 vs. 2), multiple cerebral microbleeds (CMBs; 85% vs. 40%), and anterior temporal white matter hyperintensity (WMH; 47% vs. 14%). Multivariable analysis showed that aDWI+ lesions were associated with anterior temporal WMH (odds ratio 5.7, 95% confidence interval 1.5–21.0) after adjusting for multiple lacunes, multiple CMBs, and total WMH score. Compared to sDWI+ lesions, aDWI+ lesions were more often small infarcts (<1 cm; 89% vs. 23%) and less likely to involve the corticospinal tract (11% vs. 96%). Among the 11 aDWI+ lesions with follow‐up magnetic resonance imaging, seven became microinfarcts, three became lacunes, and one disappeared. Conclusions: aDWI+ lesions in CADASIL are not uncommon and are associated with higher burdens of small vessel disease and anterior temporal WMH. Further research is needed to assess their long‐term impact on CADASIL. [ABSTRACT FROM AUTHOR]

Irritability, inattention, and hyperactivity, which are common presentations of childhood psychopathology, have been associated with perturbed white matter microstructure. However, similar tracts have been implicated across these phenotypes; such non-specificity could be rooted in their high co-occurrence. To address this problem, we use a bifactor approach parsing unique and shared components of irritability, inattention, and hyperactivity, which we then relate to white matter microstructure. We developed a bifactor model based on the Conners Comprehensive Behavioral Rating Scale in a sample of youth with no psychiatric diagnosis or a primary diagnosis of attention-deficit/hyperactivity disorder or disruptive mood dysregulation disorder (n = 521). We applied the model to an independent yet sociodemographically and clinically comparable sample (n = 152), in which we tested associations between latent variables and fractional anisotropy (FA). The bifactor model fit well (comparative fit index = 0.99; root mean square error of approximation = 0.07). The shared factor was positively associated with an independent measure of impulsivity (ρ S = 0.88, p FDR <.001) and negatively related to whole-brain FA (r = −0.20), as well as FA of the corticospinal tract (all p FWE <.05). FA increased with age and deviation from this curve, indicating that altered white matter maturation was associated with the hyperactivity-specific factor (r = −0.16, p FWE <.05). Inattention-specific and irritability-specific factors were not linked to FA. Perturbed white matter microstructure may represent a shared neurobiological mechanism of irritability, inattention, and hyperactivity related to heightened impulsivity. Furthermore, hyperactivity might be uniquely associated with a delay in white matter maturation. In this study, researchers developed a model identifying shared aspects of key symptoms of disruptive mood dysregulation disorder (DMDD) and attention-deficit hyperactivity disorder (ADHD), more specifically irritability, inattention, and hyperactivity. In 521 participants, impulsivity emerged as a shared factor. Applied to 152 youth with brain imaging data, shared impulsivity, not specific symptoms, related to atypical brain structure. Additionally, hyperactivity was linked to delayed white matter maturation. Study findings suggest this approach might identify mechanisms of these childhood disorders that remain hidden when relying on traditional diagnostic categories. [ABSTRACT FROM AUTHOR]

Objective: to study the pyramidal tract in patients with highly active multiple sclerosis (HAMS) during treatment switching from first-line MS therapy to second-line therapy due to suboptimal response.Material and methods. 24 patients with HAMS were analyzed. Depending on the severity of pyramidal functional system (PFS) impairment according to EDSS, patients were divided into 2 groups; group 1 — 17 patients with an EDSS score of 0—2.5 points, group 2 — 7 patients with an EDSS score of ≥3 points. All patients underwent MRI of the brain according to the standard protocol. The diffusion tensor images (DTI) were processed using the DTI FiberTrak software.Results. The volume of the pyramidal tract was decreased in patients in group 2 (p

Background: Hereditary Spastic Paraplegias (HSP) are genetic neurodegenerative disorders affecting the corticospinal tract. No established neuroimaging biomarker is associated with this condition. Methods: A total of 46 patients affected by HSP, genetically and clinically evaluated and tested with SPRS scores, and 46 healthy controls (HC) matched by age and gender underwent a single-voxel Magnetic Resonance Spectroscopy sampling (MRS) of bilateral pre-central and pre-frontal regions. MRS data were analyzed cross-sectionally (at T0 and T1) and longitudinally (T0 vs. T1). Results: Statistically significant data showed that T0 mI/Cr in the pre-central areas of HSP patients was higher than in HC. In the left (L) pre-central area, NAA/Cr was significantly lower in HSP than in HC. In the right (R) pre-frontal area, NAA/Cr was significantly lower in HSP patients than in HC. HSP SPG4 subjects had significantly lower Cho/Cr concentrations in the L pre-central area compared to HC. Among the HSP subjects, non-SPG4 patients had significantly higher mI/Cr in the L pre-central area compared to SPG4 patients. In the R pre-frontal area, NAA/Cr was reduced, and ml/Cr was higher in non-SPG4 patients compared to SPG4 patients. Comparing "pure" and "complex" forms, NAA/Cr was higher in pHSP than in cHSP in the R pre-central and R pre-frontal areas. The longitudinal analysis, which involved fewer patients (n = 30), showed an increase in mI/Cr concentration in the L pre-frontal area among HSP subjects with respect to baseline. The patients had significantly higher SPRS scores at follow-up, with a significant positive correlation between SPRS scores and mI/Cr in the L precentral area, while in bilateral pre-frontal areas, lower SPRS scores corresponded to higher NAA/Cr concentrations. To explore the discriminating power of MRS in correctly identifying HSP and controls, an inference tree methodology classified HSP subjects and controls with an overall accuracy of 73.9%, a sensitivity of 87.0%, and a specificity of 60.9%. Conclusion: This pilot study indicates that brain MRS is a valuable approach that could potentially serve as an objective biomarker in HSP. [ABSTRACT FROM AUTHOR]

The use of diffusion tensor imaging (DTI) has seen significant development over the last two decades, in particular with the development of the tractography of association tracts for preoperative planning of surgery. However, projection tracts are difficult to differentiate from one another and tractography studies have failed to reconstruct these ascending/descending pathways from/to the spinal cord. The present study proposes an atlas of regions of interest (ROIs) designed specifically for projection tracts tractography. Forty‐nine healthy subjects were included in this prospective study. Brain DTI was acquired using the same 3 T MRI scanner, with 32 diffusion directions. Distortions were corrected using the FSL software package. ROIs were drawn using the anterior commissure (AC)–posterior commissure (PC) line on the following landmarks: the pyramid for the corticospinal tract, the medio‐caudal part of the red nucleus for the rubrospinal tract, the pontine reticular nucleus for corticoreticular tract, the superior and inferior cerebellar peduncles for, respectively, the anterior and posterior spinocerebellar tract, the gracilis and cuneatus nucleus for the dorsal columns, and the ventro‐posterolateral nucleus for the spinothalamic tract. Fiber tracking was performed using a deterministic algorithm using DSI Studio software. ROI coordinates, according to AC–PC line, were given for each tract. Tractography was obtained for each tract, allowing tridimensional rendering and comparison of tracking metrics between tracts. The present study reports the accurate design of specific ROIs for tractography of each projection tract. This could be a useful tool in order to differentiate projection tracts at the spinal cord level. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool with potential for managing neuromuscular fatigue, possibly due to alterations in corticospinal excitability. However, inconsistencies in intra- and inter- individual variability responsiveness to tDCS limit its clinical use. Emerging evidence suggests harnessing homeostatic metaplasticity induced via tDCS may reduce variability and boost its outcomes, yet little is known regarding its influence on neuromuscular fatigue in healthy adults. We explored whether cathodal tDCS (ctDCS) prior to exercise combined with anodal tDCS (atDCS) could augment corticospinal excitability and attenuate neuromuscular fatigue. 15 young healthy adults (6 males, 22 ± 4 years) participated in four pseudo-randomised neuromodulation sessions: sham stimulation prior and during exercise, sham stimulation prior and atDCS during exercise, ctDCS prior and atDCS during exercise, ctDCS prior and sham stimulation during exercise. The exercise constituted an intermittent maximal voluntary contraction (MVC) of the right first dorsal interosseous (FDI) for 10 min. Neuromuscular fatigue was quantified as an attenuation in MVC force, while motor evoked potential (MEP) amplitude provided an assessment of corticospinal excitability. MEP amplitude increased during the fatiguing exercise, whilst across time, force decreased. There were no differences in MEP amplitudes or force between neuromodulation sessions. These outcomes highlight the ambiguity of harnessing metaplasticity to ameliorate neuromuscular fatigue in young healthy individuals. [ABSTRACT FROM AUTHOR]

Intermuscular coupling reflects the corticospinal interaction associated with the control of muscles. Nevertheless, the deterioration of intermuscular coupling caused by stroke has not received much attention. The purpose of this study was to investigate the effect of myoelectric-controlled interface (MCI) dimensionality on the intermuscular coupling after stroke. In total, ten age-matched controls and eight stroke patients were recruited and executed elbow tracking tasks within 1D or 2D MCI. Movement performance was quantified using the root mean square error (RMSE). Wavelet coherence was used to analyze the intermuscular coupling in alpha band (8–12 Hz) and beta band (15–35 Hz). The results found that smaller RMSE of antagonist muscles was observed in both groups within 2D MCI compared to 1D MCI. The alpha-band wavelet coherence was significantly lower in the patients compared to the controls during elbow extension. Furthermore, a decreased alpha-band and beta-band wavelet coherence was observed in the controls and stroke patients, as the dimensionality of MCI increased. These results may suggest that stroke-related neural impairments deteriorate the motor performance and intermuscular coordination pattern, and, further, that MCI holds promise as a novel effective tool for rehabilitation through the direct modulation of muscle activation pattern. [ABSTRACT FROM AUTHOR]

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive multisystem neurologic disorder caused by biallelic intronic repeats in RFC1. Although the phenotype of CANVAS has been expanding via diagnostic case accumulation, there are scant pedigree analyses to reveal disease penetrance, intergenerational fluctuations in repeat length, or clinical phenomena (including heterozygous carriers). We identified biallelic RFC1 ACAGG expansions of 1000 ~ repeats in three affected siblings having sensorimotor neuronopathy with spinocerebellar atrophy initially presenting with painful muscle cramps and paroxysmal dry cough. They exhibit almost homogeneous clinical and histopathological features, indicating motor neuronopathy. Over 10 years of follow-up, painful intractable muscle cramps ascended from legs to trunks and hands, followed by amyotrophy and subsequent leg pyramidal signs. The disease course combined with the electrophysical and imagery data suggest initial and prolonged hyperexcitability and the ensuing spinal motor neuron loss, which may progress from the lumbar to the rostral anterior horns and later expand to the corticospinal tract. Genetically, heterozygous ACAGG expansions of similar length were transmitted in unaffected family members of three successive generations, and some of them experienced muscle cramps. Leukocyte telomere length assays revealed comparatively shorter telomeres in affected individuals. This comprehensive pedigree analysis demonstrated a non-anticipating ACAGG transmission and high penetrance of manifestations with a biallelic state, especially motor neuronopathy in which muscle cramps serve as a prodromal and disease progress marker. CANVAS and RFC1 spectrum disorder should be considered when diagnosing lower dominant motor neuron disease, idiopathic muscle cramps, or neuromuscular hyperexcitability syndromes. [ABSTRACT FROM AUTHOR]

This study aims to explore the link between Apo-E, brain white matter, and suicide in patients with major depressive disorder (MDD) to investigate the potential neuroimmune mechanisms of Apo-E that may lead to suicide. Thirty-nine patients with MDD (22 patients with suicidality) and 57 age, gender, and education-matched healthy controls participated in this study, provided plasma Apo-E samples, and underwent diffusion tensor imaging scans. Plasma Apo-E levels and white matter microstructure were analyzed among the MDD with suicidality, MDD without suicidality, and HC groups using analysis of variance with post hoc Bonferroni correction and tract-based spatial statistics (TBSS) with threshold-free cluster enhancement correction. Mediation analysis investigated the relationship between Apo-E, brain white matter, and suicidality in MDD. The MDD with suicidality subgroup had higher depressive and suicide scores, longer disease course, and lower plasma Apo-E levels than MDD without suicidality. TBSS revealed that the MDD non-suicide subgroup showed significantly increased mean diffusivity in the left corticospinal tract and body of the left corpus callosum, as well as increased axial diffusivity in the left anterior corona radiata and the right posterior thalamic radiation compared to the suicidal MDD group. The main finding was that the increased MD of the left corticospinal tract contributed to the elevated suicide score, with Apo-E mediating the effect. Preliminary result that Apo-E's mediating role between the left corticospinal tract and the suicide factor suggests the neuroimmune mechanism of suicide in MDD. The study was registered on ClinicalTrials.gov (NCT03790085). [ABSTRACT FROM AUTHOR]

We investigate the etiology of amyotrophic lateral sclerosis (ALS) in a 35-year-old woman presenting with progressive weakness in her left upper limb. Prior to sequencing, a comprehensive neurological work-up was performed, including neurological examination, electrophysiology, biomarker assessment, and brain and spinal cord MRI. Six months before evaluation, the patient experienced weakness and atrophy in her left hand, accompanied by brisk reflexes and Hoffman sign in the same arm. Electroneuromyography revealed lower motor neuron involvement in three body regions. Neurofilament light chains were elevated in her cerebrospinal fluid. Brain imaging showed asymmetrical T2 hyperintensity of the corticospinal tracts and T2 linear hypointensity of the precentral gyri. Trio genome sequencing identified a likely pathogenic de novo variant in the KIF1A gene (NM_001244008.2): c.574A>G, p.(Ile192Val). Pathogenic variants in KIF1A have been associated with a wide range of neurological manifestations called KIF1A-associated neurological diseases (KAND). This report describes a likely pathogenic de novo variant in KIF1A associated with ALS, expanding the phenotypic spectrum of KAND and our understanding of the pathophysiology of ALS. [ABSTRACT FROM AUTHOR]

Objectives: Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy is a novel, minimally invasive ablative treatment for essential tremor (ET). The use of a four-tract probabilistic tractography technique, targeting the intersection between the dentato-rubro-thalamic tracts (both decussating and non-decussating), while evaluating the corticospinal tract and the medial lemniscus, may obtain immediate clinical results with reduced adverse events. Our aim is to present our experience with the four-tract technique for patients undergoing ET treatment with MRgFUS. Methods: Retrospective analysis of a prospective database of consecutive patients undergoing ET treatment in a single center from February 2022 to February 2023. Procedural parameters were collected, and tremor improvement was assessed with the Clinical Rating Scale for Tremor (CRST) at baseline and at 3 and 6 months. Adverse events were also reported. Results: Forty-three patients (median age, 72 years [interquartile range, 66–76]; 22 females) were evaluated. Tremor improved significatively in all CRST subsections at 3 months, including the CRST part A + B treated hand tremor (22 [19–27] vs 4 [2–7], p < 0.001) and CRST part C (16 [13–19] vs 3 [1–4], p < 0.001). Differences persisted significant at 6 months. Adverse events were few (4.1% of paresthesias and 12.5% of objective gait disturbance at follow-up) and recorded as mild. The median number of sonications was 7 [6–8] and mean operative time 68.7 ± 24.2 min. Conclusion: Our data show support for the feasibility and benefits of systematic targeting approach with four-tract probabilistic tractography for treating ET using MRgFUS. Clinical relevance statement: An approach with four-tract probabilistic tractography for treating essential tremor (ET) patients with magnetic resonance–guided focused ultrasound decreases interindividual variability with good clinical outcomes, low number of sonications, few adverse effects, and short procedure times. Key Points: • The optimal target for the treatment of essential tremor with MR-guided focused ultrasound remains unknown. • Four-tract probabilistic tractography is a feasible technique that reduces interindividual variability, with good clinical results, few side effects, and short operative time. • The four-tract tractography approach can be performed using different MRI scanners and post-processing software in comparison with the initial description of the technique. [ABSTRACT FROM AUTHOR]

Introduction: Intracerebral hemorrhage (ICH) is a severe manifestation of stroke, demonstrating notably elevated global mortality and morbidity. Thus far, effective therapeutic strategies for ICH have proven elusive. Currently, minimally invasive techniques are widely employed for ICH management, particularly using endoscopic hematoma evacuation in cases of deep ICH. Exploration of strategies to achieve meticulous surgery and diminish iatrogenic harm, especially to the corticospinal tract, with the objective of enhancing the neurological prognosis of patients, needs further efforts. Methods: We comprehensively collected detailed demographic, clinical, radiographic, surgical, and postoperative treatment and recovery data for patients who underwent endoscopic hematoma removal. This thorough inclusion of data intends to offer a comprehensive overview of our technical experience in this study. Results: One hundred fifty-four eligible patients with deep supratentorial intracerebral hemorrhage who underwent endoscopic hematoma removal were included in this study. The mean hematoma volume was 42 ml, with 74 instances of left-sided hematoma and 80 cases of right-sided hematoma. The median Glasgow Coma Scale (GCS) score at admission was 10 (range from 4 to 15), and the median time from symptom onset to surgery was 18 (range 2 to 96) h. The mean hematoma clearance rate was 89%. The rebleeding and mortality rates within 1 month after surgery were 3.2% and 7.8%, respectively. At the 6-month mark, the proportion of patients with modified Rankin Scale (mRS) scores of 0–3 was 58.4%. Conclusion: Both the reduction of surgery-related injury and the protection of the residual corticospinal tract through endoscopic hematoma removal may potentially enhance neurological functional outcomes in patients with deep ICH, warranting validation in a forthcoming multicenter clinical study. [ABSTRACT FROM AUTHOR]

D-waves (also called direct waves) result from the direct activation of fast-conducting, thickly myelinated corticospinal tract (CST) fibres after a single electrical stimulus. During intraoperative neurophysiological monitoring, D-waves are used to assess the long-term motor outcomes of patients undergoing surgery for intramedullary spinal cord tumours, selected cases of intradural extramedullary tumours and surgery for syringomyelia. In the present manuscript, we discuss D-wave monitoring and its role as a tool for monitoring the CST during spinal cord surgery. We describe the neurophysiological background and provide some recommendations for recording and stimulation, as well as possible future perspectives. Further, we introduce the concept of anti D-wave and present an illustrative case with successful recordings. [ABSTRACT FROM AUTHOR]

Studies suggest that amyotrophic lateral sclerosis (ALS) compromises the integrity of white matter fiber tracts, primarily affecting motor fibers. However, it remains uncertain whether the integrity of these fibers influences the risk of ALS. We performed bidirectional two-sample Mendelian randomization (MR) and multivariable MR analyses to evaluate the associative relationships between the integrity of fiber tracts [including the corticospinal tract (CST) and corpus callosum (CC)] and the risk of ALS. Genetic instrumental variables for specific fiber tracts were obtained from published genome-wide association studies (GWASs), including 33,292 European individuals from five diffusion magnetic resonance imaging (dMRI) datasets. Summary-level GWAS data for ALS were derived from 27,205 ALS patients and 110,881 controls. The MR results suggested that an increase in the first principal component (PC1) of fractional anisotropy (FA) in the genu of the CC (GCC) was correlated with an increased risk of ALS (PFDR = 0.001, odds ratio = 1.363, 95% confidence interval 1.178–1.577). Although other neuroimaging phenotypes [mean diffusivity in the CST, radial diffusivity (RD) in the CST, FA in the GCC, PC1 in the body of the CC (BCC), PC1 in the CST, and RD in the GCC] did not pass correction, they were also considered to have suggestive associations with the risk of ALS. No evidence revealed that ALS caused changes in the integrity of fiber tracts. In summary, the results of this study provide genetic support for the potential association between the integrity of specific fiber tracts and the risk of ALS. Greater fiber integrity in the GCC and BCC may be a risk factor for ALS, while greater fiber integrity in the CST may have a protective effect on ALS. This study provides insights into ALS development. [ABSTRACT FROM AUTHOR]

Background: To investigate the association between white matter changes and ventricular expansion in idiopathic normal pressure hydrocephalus (iNPH) based on diffusion spectrum imaging (DSI). Methods: We included 32 patients with iNPH who underwent DSI using a 3T MRI scanner. The lateral ventricles were manually segmented, and ventricular volumes were measured. Two methods were utilised in the study: manual region-of-interest (ROI) delineation and tract diffusion profile analysis. General fractional anisotropy (GFA) and fractional anisotropy (FA) were extracted in different white matter regions, including the bilateral internal capsule (anterior and posterior limbs) and corpus callosum (body, genu, and splenium) with manual ROI delineation. The 18 main tracts in the brain of each patient were extracted; the diffusion metrics of 100 equidistant nodes on each fibre were calculated, and Spearman's correlation coefficient was used to determine the correlation between diffusion measures and ventricular volume of iNPH patients. Results: The GFA and FA of all ROI showed no significant correlation with lateral ventricular volume. However, in the tract diffusion profile analysis, lateral ventricular volume was positively correlated with part of the cingulum bundle, left corticospinal tract, and bilateral thalamic radiation posterior, whereas it was negatively correlated with the bilateral cingulum parahippocampal (all p < 0.05). Conclusions: The effect of ventricular enlargement in iNPH on some white matter fibre tracts around the ventricles was limited and polarizing, and most white matter fibre tract integrity changes were not associated with ventricular enlargement; this reflects that multiple pathological mechanisms may have been combined to cause white matter alterations in iNPH. [ABSTRACT FROM AUTHOR]

Background: Tic disorder is a neuropsychiatric disorder characterized by involuntary movements or vocalizations. Previous studies utilizing diffusion-weighted imaging to explore white-matter alterations in tic disorders have reported inconsistent results regarding the affected tracts. We aimed to address this gap by employing a novel tractography technique for more detailed analysis. Methods: We analyzed MRI data from 23 children with tic disorders and 23 healthy controls using TRActs Constrained by UnderLying Anatomy (TRACULA), an advanced automated probabilistic tractography method. We examined fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity, and mean diffusivity in 42 specific significant white matter tracts. Results: Our findings revealed notable differences in the children with tic disorders compared to the control group. Specifically, there was a significant reduction in FA in the parietal part and splenium of the corpus callosum and the left corticospinal tract. Increased RD was observed in the temporal and splenium areas of the corpus callosum, the left corticospinal tract, and the left acoustic radiation. A higher mean diffusivity was also noted in the left middle longitudinal fasciculus. A significant correlation emerged between the severity of motor symptoms, measured by the Yale Global Tic Severity Scale, and FA in the parietal part of the corpus callosum, as well as RD in the left acoustic radiation. Conclusion: These results indicate a pattern of reduced interhemispheric connectivity in the corpus callosum, aligning with previous studies and novel findings in the diffusion indices changes in the left corticospinal tract, left acoustic radiation, and left middle longitudinal fasciculus. Tic disorders might involve structural abnormalities in key white matter tracts, offering new insights into their pathogenesis. [ABSTRACT FROM AUTHOR]

Stroke-caused synergies may result from the preferential use of the reticulospinal tract (RST) due to damage to the corticospinal tract. The RST branches multiple motoneuron pools across the arm together resulting in gross motor control or abnormal synergies, and accordingly, the controllability of individual muscles decreases. However, it is not clear whether muscles involuntarily activated by abnormal synergy vary depending on the muscles voluntarily activated when motor commands descend through the RST. Studies showed that abnormal synergies may originate from the merging and reweighting of synergies in individuals without neurological deficits. This leads to a hypothesis that those abnormal synergies are still selectively excited depending on the context. In this study, we test this hypothesis, leveraging the Fugl-Meyer assessment that could characterize the neuroanatomical architecture in individuals with a wide range of impairments. We examine the ability to perform an out-of-synergy movement with the flexion synergy caused by either shoulder or elbow loading. The results reveal that about 14% [8/57, 95% confidence interval (5.0%, 23.1%)] of the participants with severe impairment (total Fugl-Meyer score <29) in the chronic phase (6 months after stroke) are able to keep the elbow extended during shoulder loading and keep the shoulder at neutral during elbow loading. Those participants underwent a different course of neural reorganization, which enhanced abnormal synergies in comparison with individuals with mild impairment (P < 0.05). These results provide evidence that separate routes and synergy modules to motoneuron pools across the arm might exist even if the motor command is mediated possibly via the RST. NEW & NOTEWORTHY: We demonstrate that abnormal synergies are still selectively excited depending on the context. [ABSTRACT FROM AUTHOR]

The flexion synergy and extension synergy are a representative consequence of a stroke and appear in the upper extremity and the lower extremity. Since the ipsilesional corticospinal tract (CST) is the most influential neural pathway for both extremities in motor execution, damage by a stroke to this tract could lead to similar motor pathological features (e.g., abnormal synergies) in both extremities. However, less attention has been paid to the interlimb correlations in the flexion synergy and extension synergy across different recovery phases of a stroke. We used results of the Fugl–Meyer assessment (FMA) to characterize those correlations in a total of 512 participants with hemiparesis after stroke from the acute phase to 1 year. The FMA provides indirect indicators of the degrees of the flexion synergy and extension synergy after stroke. We found that, generally, strong interlimb correlations (r > 0.65 with all P values < 0.0001) between the flexion synergy and extension synergy appeared in the acute-to-subacute phase (<90 days). However, the correlations of the lower-extremity extension synergy with the upper-extremity flexion synergy and extension synergy decreased (down to r = 0.38) 360 days after stroke (P < 0.05). These results suggest that the preferential use of alternative neural pathways after damage by a stroke to the CST enhances the interlimb correlations between the flexion synergy and extension synergy. At the same time, the results imply that the recovery of CST integrity or/and the fragmentation (remodeling) of the alternative neural substrates in the chronic phase may contribute to diversity in neural pathways in motor execution, eventually leading to reduced interlimb correlations. NEW & NOTEWORTHY: For the first time, this article addresses the asynchronous relationships in the strengths of flexion and extension synergy expressions between the paretic upper extremity and lower extremity across various phases of stroke. [ABSTRACT FROM AUTHOR]

Background. There is as yet no uniform view as to the effectiveness of fluorescence microscopy (FM) in patients with tumors located near functionally important areas of the brain (FAB), where the surgeon can elect to terminate resection because of a high risk of increasing neurological deficit. Task. To evaluate the effectiveness of FM in removing gliomas near the motor cortex (MC) and corticospinal tract (CST). Methods. A total of 108 adult patients with gliomas near the MC and CST who underwent surgery with neurophysiological monitoring were divided into two groups depending on the use of FM: a control group (34 patients without FM) and a study group (62 patients with FM). Results. The extent of resection and the frequency of neurological deficits in the postoperative period were not significantly different in the groups studied. Conclusions. Despite the absence of any statistically significant between-group difference, FM may be of value as a component of intraoperative monitoring in this group of patients. [ABSTRACT FROM AUTHOR]