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Stroke patients commonly face challenges during magnetic resonance imaging (MRI) examinations due to involuntary movements. This study aims to overcome these challenges by utilizing multiple overlapping-echo detachment (MOLED) quantitative technology. Through this technology, we also seek to detect microstructural changes of the normal-appearing corticospinal tract (NA-CST) in subacute-chronic stroke patients. 79 patients underwent 3.0 T MRI scans, including routine scans and MOLED technique. A deep learning network was utilized for image reconstruction, and the accuracy, reliability, and resistance to motion of the MOLED technique were validated on phantoms and volunteers. Subsequently, we assessed motor dysfunction severity, ischemic lesion volume, T 2 values of the bilateral NA-CST, and the T 2 ratio (rT 2) between the ipsilesional and contralesional NA-CST in patients. The MOLED technique showed high accuracy (P < 0.001) and excellent repeatability, with a mean coefficient of variation (CoV) of 1.11%. It provided reliable quantitative results even under head movement, with a mean difference (Mean diff) = 0.28% and a standard deviation difference (SD diff) = 1.34%. Additionally, the T 2 value of the ipsilesional NA-CST was significantly higher than contralesional side (P < 0.001), and a positive correlation was observed between rT 2 and the severity of motor dysfunction (r s = 0.575, P < 0.001). Furthermore, rT 2 successfully predicted post-stroke motor impairment, with an area under the curve (AUC) was 0.883. The MOLED technique offers significant advantages for quantitatively imaging stroke patients with involuntary movements. Additionally, T 2 mapping from MOLED can detect microstructural changes in the NA-CST, potentially aiding in monitoring stroke-induced motor impairment. [ABSTRACT FROM AUTHOR]

Gliomas adjacent to the corticospinal tract (CST) should be carefully resected to preserve motor function while achieving maximal surgical resection. Modern high-field intraoperative magnetic resonance imaging (iMRI) enables precise visualization of the residual tumor and intraoperative tractography. We prospectively evaluated the extent of resection and distance between the tumor resection cavity and CST using 3-T iMRI combined with motor evoked potentials (MEP) in glioma surgery. Participants comprised patients who underwent surgery for solitary supratentorial glioma located within 10 mm of the CST. All cases underwent surgery using neuronavigation with overlaid CST under MEP monitoring. The correlation between distance from CST and transcortical MEP amplitude was calculated using Spearman rank correlation. Among the 63 patients who underwent surgery, 27 patients were enrolled in the study. Gross total resections were achieved in 26 of the 27 cases. Volumetric analysis showed the extent of resection was 98.6%. Motor function was stable or improved in 24 patients (Stable/Improved group) and deteriorated in 3 patients (Deteriorated group). All patients in the Deteriorated group showed motor deficit before surgery. Mean intraoperative minimal distance was significantly longer in the Stable/Improved group (7.3 mm) than in the Deteriorated group (1.1 mm; P < 0.05). MEP amplitude correlated with minimal distance between the resection cavity and CST (R = 0.64). Resection of gliomas adjacent to CST with a navigation system using 3-T iMRI could result in an ultimate EOR >98%. The combination of intraoperative tractography and MEP contributes to maximal removal of motor-eloquent gliomas. [ABSTRACT FROM AUTHOR]

[Display omitted] • Our findings do not support the use of rTMS as a standalone treatment for CLBP. • Top-down and bottom-up interventions might trigger a distinct priming mechanism. • Our study contributed to optimizing treatment strategies for CLBP. The study aims to explore the effects of combining repetitive transcranial magnetic stimulation (rTMS) with sling exercise (SE) intervention in patients with chronic low back pain (CLBP). This approach aims to directly stimulate brain circuits and indirectly activate trunk muscles to influence motor cortex plasticity. However, the impact of this combined intervention on motor cortex organization and clinical symptom improvement is still unclear, as well as whether it is more effective than either intervention alone. To investigate this, patients with CLBP were randomly assigned to three groups: SE/rTMS, rTMS alone, and SE alone. Motor cortical organization, numerical pain rating scale (NPRS), Oswestry Disability Index (ODI), and postural balance stability were measured before and after a 2-week intervention. The results showed statistically significant differences in the representative location of multifidus on the left hemispheres, as well as in NPRS and ODI scores, in the combined SE/rTMS group after the intervention. When compared to the other two groups, the combined SE/rTMS group demonstrated significantly different motor cortical organization, sway area, and path range from the rTMS alone group, but not from the SE alone group. These findings highlight the potential benefits of a combined SE/rTMS intervention in terms of clinical outcomes and neuroadaptive changes compared to rTMS alone. However, there was no significant difference between the combined intervention and SE alone. Therefore, our research does not support the use of rTMS as a standalone treatment for CLBP. Our study contributed to optimizing treatment strategies for individuals suffering from CLBP. [ABSTRACT FROM AUTHOR]

[Display omitted] • Axon guidance molecules (AGM) regulate neuronal development. • AGMs play a crucial role in directing axons to their final destinations. • After CNS traumas, defects in these processes affect neuronal circuit rebuilding. • AGMs expression in spinal cord circuits can help find novel therapeutic targets. Axon guidance molecules (AGM) are critical regulators of neural development and play a vital role in guiding axons to their target regions during spinal cord development. The correct wiring of neural circuits depends on these molecules' precise expression and function. Defects in axonal pathfinding, growth cone navigation, axonal branching, and synapse formation have far-reaching implications for neuronal circuit construction and function after CNS traumas, such as spinal cord injury (SCI), which affect the expression or activity of AGM. Ascending and descending paths in the spinal cord have been found to include many AGM, including Netrins, Slits, Semaphorins (Sema), Ephrins, and their receptors. In contrast to the repulsive signals like Slits and Semaphorins, which restrict axonal growth and guide axons away from unsuitable locations, Netrins are appealing guidance cues that encourage axonal growth and guidance. Defects in motor function and sensory processing can result from changes in the expression or activity of Ephrins or their receptors, which play an essential role in axonal guidance and synaptic plasticity in the spinal cord. Herein, we highlighted the expressions, functions, and mechanisms of AGM in ascending and descending spinal cord tracts, which can help us identify novel therapeutic targets to improve axonal regeneration and functional recovery after SCI. [ABSTRACT FROM AUTHOR]

Neural activity helps construct neural circuits during development and this function is leveraged by neuromodulation protocols to promote connectivity and repair in maturity. Neuromodulation targeting the motor cortex (MCX) strengthens connections for evoking muscle contraction (MEPs). Mechanisms include promoting local MCX and corticospinal tract (CST) synaptic efficacy and also axon terminal structural changes. In this study, we address the question of potential causality between neuronal activation and the neuronal structural response. We used patterned optogenetic activation (ChR2-EYFP), daily for 10-days, to deliver intermittent theta burst stimulation (iTBS) to activate MCX neurons within the forelimb representation in healthy rats, while differentiating them from neurons in the same population that were not activated. We used chemogenetic DREADD activation to produce a daily period of non-patterned neuronal activation. We found a significant increase in CST axon length, axon branching, contacts targeted to a class of premotor interneuron (Chx10), as well as projections into the motor pools in the ventral horn in optically activated but not neighboring non-activated neurons. A period of 2-h of continuous activation daily for 10 days using DREADD chemogenetic activation with systemic clozapine N-oxide (CNO) administration also increased CST axon length and branching, but not the ventral horn and Chx10 targeting effects. Both patterned optical and chemogenetic activation reduced MCX MEP thresholds. Our findings show that targeting of CST axon sprouting is dependent on patterned activation, but that CST spinal axon outgrowth and branching are not. Our optogenetic findings, by distinguishing optically activated and non-activated CST axons, suggests that the switch for activity-dependent axonal outgrowth is neuron-intrinsic. • Daily patterned optical activation produced CST axon sprouting and enhanced branching. • Non-stimulated neighboring neurons did not express the growth response. • Imaging shows causality between optical activation and axon structural changes. • Chemogenetic activation produced enhanced activity also resulting in axon growth response. • Patterned optical, but not chemogenetic, activation targeted sprouting to premotor interneurons and to motor pools. [ABSTRACT FROM AUTHOR]

It is known that any surgery to the nervous system poses risks to neural structures and their surrounding structures. These mechanisms of injury are the result of mechanical manipulations, haemodynamic alterations, chemical or thermal injuries. Intraoperative neurophysiological monitoring (IONM), using various modalities, is employed to facilitate the assessment of the functional integrity of neural structures, and it is used to provide a real-time alerting system when changes caused by surgically induced insults are detected. The primary goal of IONM is reducing the risk of postoperative neurological deficits during these surgical procedures. It is used to provide information that allows the surgeon to correct any surgical interventions that may have compromised these systems and this also in turn provides guidance on what neurological deficits to anticipate postoperatively. Apart from being utilized as an alerting system to avoid catastrophic outcomes, IONM also assists as a guidance system using stimulation techniques to map out eloquent areas within the cortex, allowing identification of specific neuronal structures, particularly when landmarks cannot be easily recognized due to infiltration by pathological lesions. In this article, we focus on updating our previous paper published in 2019 and again, to provide attention to the various neurophysiological modalities that are employed in IONM. We will look at the basic underlying physiological principles and their individual indications for use clinically. We will explain the information that each modality provides. Importantly, and the primary reason for this article, we look at the various anaesthetic agents, their effects on each neurophysiological modality and other anaesthetic considerations such as haemodynamic and temperature effects. We will also recommend the use of an alert checklist for the multidisciplinary team should an intraoperative alert be issued during surgical procedures. [ABSTRACT FROM AUTHOR]

The corticospinal tract (CST), which plays a major role in the control of voluntary limb movements, arises from multiple motor- and somatosensory-related areas in monkeys. Although the cortical origin and quantitative differences in CSTs among the cortical areas are well-documented in monkeys, they are unclear in humans. We quantitatively investigated the CSTs from the cerebral cortex to the cervical cord in healthy volunteers using fiber tractography of diffusion-weighted magnetic resonance imaging. The corticospinal (CS) streamlines arose from nine cortical areas: primary motor area (mean ± SD = 49.71 ± 1.61%), dorsal (16.33 ± 1.37%) and ventral (11.02 ± 0.90%) premotor cortex, supplementary motor area (5.14 ± 0.36%), pre-supplementary motor area (2.46 ± 0.26%), primary somatosensory cortex (11.06 ± 0.91%), Brodmann area 5 (0.88 ± 0.09%), caudal cingulate zone (1.70 ± 0.30%), and posterior part of the rostral cingulate zone (1.70 ± 0.34%). In all cortical areas, the number of CS streamlines gradually decreased from the rostral to caudal spinal segments, but the proportion was maintained throughout the cervical cord. Over 75% of CS streamlines arose from the lateral surface of the frontal lobe, which may explain the voluntary control of dexterous and flexible limb movements in humans. (197/200 words) • Nine cortical regions are the origins of corticospinal tract in humans. • Over 75% of corticospinal streamlines arose from the lateral frontal lobe. • CS streamlines gradually decreased from the rostral to caudal spinal segments. [ABSTRACT FROM AUTHOR]

Magnetic resonance (MR) imaging (MRI) is commonly used to diagnose, assess and monitor stroke. Accurate and timely segmentation of stroke lesions provides the anatomico-structural information that can aid physicians in predicting prognosis, as well as in decision making and triaging for various rehabilitation strategies. To segment stroke lesions, MR protocols, including diffusion-weighted imaging (DWI) and T2-weighted fluid attenuated inversion recovery (FLAIR) are often utilized. These imaging sequences are usually acquired with different spatial resolutions due to time constraints. Within the same image, voxels may be anisotropic, with reduced resolution along slice direction for diffusion scans in particular. In this study, we evaluate the ability of 2D and 3D U-Net Convolutional Neural Network (CNN) architectures to segment ischemic stroke lesions using single contrast (DWI) and dual contrast images (T2w FLAIR and DWI). The predicted segmentations correlate with post-stroke motor outcome measured by the National Institutes of Health Stroke Scale (NIHSS) and Fugl-Meyer Upper Extremity (FM-UE) index based on the lesion loads overlapping the corticospinal tracts (CST), which is a neural substrate for motor movement and function. Although the four methods performed similarly, the 2D multimodal U-Net achieved the best results with a mean Dice of 0.737 (95% CI: 0.705, 0.769) and a relatively high correlation between the weighted lesion load and the NIHSS scores (both at baseline and at 90 days). A monotonically constrained quintic polynomial regression yielded R2 = 0.784 and 0.875 for weighted lesion load versus baseline and 90-Days NIHSS respectively, and better corrected Akaike information criterion (AIC c) scores than those of the linear regression. In addition, using the quintic polynomial regression model to regress the weighted lesion load to the 90-Days FM-UE score results in an R2 of 0.570 with a better AIC c score than that of the linear regression. Our results suggest that the multi-contrast information enhanced the accuracy of the segmentation and the prediction accuracy for upper extremity motor outcomes. Expanding the training dataset to include different types of stroke lesions and more data points will help add a temporal longitudinal aspect and increase the accuracy. Furthermore, adding patient-specific data may improve the inference about the relationship between imaging metrics and functional outcomes. [ABSTRACT FROM AUTHOR]

This study investigates the potential of transcranial magnetic stimulation (TMS) to enhance spinal cord axon regeneration by modulating corticospinal pathways and improving motor nerve function recovery in rats with spinal cord injury (SCI). TMS is a non-invasive neuromodulation technique that generates a magnetic field to activate neurons in the brain, leading to depolarization and modulation of cortical activity. Initially utilized for brain physiology research, TMS has evolved into a diagnostic and prognostic tool in clinical settings, with increasing interest in its therapeutic applications. However, its potential for treating motor dysfunction in SCI has been underexplored. The TMS intervention group exhibited significant improvements compared to the control group across behavioral assessments, neurophysiological measurements, pathological analysis, and immunological markers. Unlike most studies that focus on localized spinal cord injury or muscle treatments, this study leverages the non-invasive, painless, and highly penetrating nature of TMS to focus on the corticospinal tracts, exploring its therapeutic potential for SCI. TMS enhances motor function recovery in rats with SCI by restoring corticospinal pathway integrity and promoting axonal regeneration. These findings highlight TMS as a promising therapeutic option for SCI patients with currently limited treatment alternatives. • TMS enhances motor function recovery in rats with spinal cord injury. • rTMS improves corticospinal pathway integrity and promotes axonal regeneration. • The study shows TMS as a non-invasive and effective treatment for SCI. • Findings suggest the potential of TMS to offer new therapeutic avenues for SCI. • Further research is needed to optimize TMS parameters and understand its mechanisms. [ABSTRACT FROM AUTHOR]

• A lower level of intracellular volume fraction in the corticospinal tract corresponded to a shorter overall survival of glioblastoma. • The prognosis differed between histological glioblastoma and molecular glioblastoma. • Glioblastoma affected side and contralateral differences are described by corticospinal tract based on multishell diffusion models. Advanced MR fiber tracking imaging reflects fiber bundle invasion by glioblastoma, particularly of the corticospinal tract (CST), which is more susceptible as the largest downstream fiber tracts. We aimed to investigate whether CST features can predict the overall survival of glioblastoma. In this prospective secondary analysis, 40 participants (mean age, 58 years; 16 male) pathologically diagnosed with glioblastoma were enrolled. Diffusion spectrum MRI was used for CST reconstruction. Fifty morphological and diffusion indicators (DTI, DKI, NODDI, MAP and Q-space) were used to characterize the CST. Optimal parameters capturing fiber bundle damage were obtained through various grouping methods. Eventually, the correlation with overall survival was determined by the hazard ratios (HRs) from various Cox proportional hazard model combinations. Only intracellular volume fraction (ICVF) and non-Gaussianity (NG) values on the affected tumor level were significant in all four groups or stratified comparisons (all P <.05). During the median follow-up 698 days, only the ICVF on the affected tumor level was independently associated with overall survival, even after adjusting for all classic prognostic factors (HR [95 % CI]: 0.611 [0.403, 0.927], P =.021). Moreover, stratification by the ICVF on the affected tumor level successfully predicted risk (P <.01) and improved the C-index of the multivariate model (from 0.695 to 0.736). This study demonstrates a relationship between NODDI-derived CST features, ICVF on the affected tumor level, and overall survival in glioblastoma. Independent of classical prognostic factors for glioblastoma, a lower ICVF on the affected tumor level might predict a lower overall survival. [ABSTRACT FROM AUTHOR]

• Developmental time course of corticomotoneuronal connections in mice was revealed. • Synaptic responses were recorded from much older motoneurons than previously. • The slice preparation procedure was improved, making recording possible beyond P40. • Direct connections increased until reaching a plateau on P8. • Direct connections decreased from P14 and were not detected after P21. We previously observed in rodents that during the 2nd postnatal week corticospinal axons make monosynaptic connections with motoneurons. Prior to that finding, it had been believed that such contacts only occur in higher primates. Although an in vitro electrophysiological study is prerequisite for studying the developmental time course of synaptic connections, the technical difficulty of reliably recording synaptic responses from spinal motoneurons in animals over 2 weeks old hampered the study. Instead, we used retrograde transsynaptic labeling with a genetically modified rabies virus to confirm the presence of direct corticomotoneuronal connections at an early developmental stage and to show that these connections were subsequently eliminated. However, determination of an accurate elimination time course and quantitative evaluation of synaptic connectivity cannot be achieved through viral-tracing experiments. For the present study, we improved the slice preparation procedure and maintenance of slice viability, which enabled us to record postsynaptic responses using the whole cell patch-clamp technique from retrogradely labeled forearm motoneurons up until postnatal week 7. We examined the extent of corticomotoneuronal monosynaptic connections and studied the time course of their accumulation and loss. Positive ratios of monosynaptic corticomotoneuronal EPSCs increased from P6 to P8 and then plateaued (P8–P13: 65%). Thereafter, the monosynaptic connections declined until P21, at which time they were no longer detected. The time course of the falling phase and elimination was confirmed by experiments using optogenetic stimulation. The timing of the elimination fell within the same range (P18-22) estimated in our earlier study using retrograde transsynaptic labeling. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) can be a useful tool for the assessment of the brain functional reorganization in subjects with hemiplegic cerebral palsy (HCP). In this review, we performed a systematic search of all studies using TMS in order to explore the neuroplastic changes that occur in HCP patients. We aimed at investigating the usefulness of TMS to explore cortical excitability, plasticity and connectivity changes in HCP. Children with HCP due to unilateral lesions of the corticospinal system had ipsilateral motor evoked potentials (MEPs) similar to those recorded contralaterally. TMS studies demonstrated that occupational and constraint-induced movement therapy were associated with significant improvements in contralateral and ipsilateral corticomotor projection patterns. In addition, after intensive bimanual therapy, children with HCP showed increased activation and size of the motor areas controlling the affected hand. A TMS mapping study revealed a mediolateral location of the upper and lower extremity map motor cortical representations. Deficits in intracortical and interhemispheric inhibitory mechanisms were observed in HCP. Early hand function impairment correlated with the extension of brain damage, number of involved areas, and radiological signs of corticospinal tract (CST) degeneration. Clinical mirror movements (MMs) correlated with disability and CST organization in subjects with HCP and a positive relationship was found between MMs and MEPs strength. Therefore, TMS studies have shed light on important pathophysiological aspects of motor cortex and CST reorganization in HCP patients. Furthermore, repetitive TMS (rTMS) might have therapeutic effects on CST activities, functional connectivity and clinical status in children with HCP. [ABSTRACT FROM AUTHOR]

• The corticospinal tract (CST) structure and function and gait were significantly altered in children with Cerebral Palsy (CP). • The structural abnormalities of CST were significantly correlated with gait impairment in some CP children with brain injury. • These findings may provide a better understanding of the mechanisms underlying gait impairment in children with CP. Corticospinal tract (CST) injury may lead to motor disorders in children with Cerebral Palsy (CP). However, the precise underlying mechanisms are still ambiguous. We aimed to characterize the CST structure and function in children with CP and determine their contributions to balance and gait impairments. Twenty-six children with spastic CP participated. Transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) were utilized to characterize CST structure and function. Common clinical measures were used to assess gait speed, endurance and balance, and mobility. CST structure and function were significantly altered in children with CP. Different abnormal patterns of CST structure were identified as either abnormal appearance of brain hemispheres (Group-1) or semi-normal CST appearance (Group-2). We found significant correlations between the DTI parameters of the more affected CST and gait features only in Group-1. CST structure and function are abnormal in children with CP and these abnormalities may contribute to balance and gait impairment in some children with CP. Our findings may lead to the development of further investigations on the mechanisms underlying gait impairment in children with CP and on decision-making for more effective rehabilitation. [ABSTRACT FROM AUTHOR]

Background: An improved understanding of the genetic determinants of Parkinson's disease (PD) in underrepresented populations, and better characterization of genotype-phenotype correlations in monogenic PD, are needed. Scarce literature exists regarding the genetic aetiology of PD in Malays, who comprise 200 million individuals in South-East Asia. Phenotypic data regarding PARK-PINK1 are also limited.Methods: A multi-ethnic cohort of PD patients from Malaysia (n = 499, including 185 Malays) were tested using a next-generation sequencing-based PD gene panel. The prevalence and clinico-radiological features of patients with the PINK1 p. Leu347Pro mutation are described. This mutation has previously only been reported in people of Filipino or Chamorro (native Guamanian) ancestry.Results: Homozygous p. Leu347Pro mutations were found in five unrelated Malay patients, yielding a prevalence of 6.9% among Malays with PD onset ≤50 years (2.7% of the Malay group overall). This variant was not detected in the homozygous state in 300 Malay controls, but two were heterozygous carriers (0.67%) indicating a relatively high population frequency in keeping with the high frequency of PARK-PINK1 among Malay patients. Interesting clinical features were observed, e.g., differences in the age at PD onset and clinical progression, despite having the same point mutations. Previously unreported brain MRI abnormalities involving the corticospinal tract and hypothalamus, and "loss of the swallow tail" sign, were documented.Conclusions: This report contributes to the very limited literature on PD genetics in the Malay population, and more broadly to the epidemiological, phenotypic and neuroimaging characterization of PARK-PINK1. It also further supports the pathogenicity of the p. Leu347Pro variant. [ABSTRACT FROM AUTHOR]

• Corticospinal tract regulates muscle activation by shifting tonic stretch-reflex thresholds. • Corticospinal modulation of muscle activation is impaired in moderate and severe stroke. • Deficits in corticospinal modulation of reflex thresholds correlated with clinical impairment. The corticospinal system (CS) regulates muscle activation through shifts in muscle-level tonic stretch-reflex thresholds (TSRT). This ability is impaired in stroke and contributes to sensorimotor impairments such as spasticity. We determined the role of CS in elbow flexor activity regulation in healthy and post-stroke subjects. We also determined whether CS modulation deficits were related to sensorimotor impairment intensity in post-stroke individuals. Seventeen healthy (59.8 ± 12.2 yr) and 27 stroke subjects (58.7 ± 10.1 yr) had transcranial magnetic stimulation (TMS) applied over the primary motor cortex (M1) flexor representation to elicit motor-evoked potentials (MEPs) in elbow flexors in different angular positions. In a subset of post-stroke subjects (n = 12), flexor TSRTs were measured in passive and active conditions, and TSRT modulation was determined. Position-related MEP amplitude modulation was similar in healthy and mild stroke subjects, while subjects with more severe stroke exhibited less consistent modulation. MEP modulation in stroke was related to clinical upper limb motor impairment, spasticity, and the ability to modulate TSRTs between passive and active elbow movements. CS output was closely related to TSRT modulation. Impairments in TSRT regulation may underlie motor deficits in moderate-to-severe post-stroke individuals. Translation of these neurophysiological findings to clinical applications may enhance post-stroke motor recovery. [ABSTRACT FROM AUTHOR]

• SSEP and tcmMEP monitoring has been employed for safe resection of intramedullary tumors. • There is good correlation between tcmMEP monitoring, CST mapping and post-operative motor outcome. • Supratentorial CST mapping thresholds depend on multiple variables. Spinal cord surgeries carry a high risk for significant neurological impairments. The initial techniques for spinal cord mapping emerged as an aid to identify the dorsal columns and helped select a safe myelotomy site in intramedullary tumor resection. Advancements in motor mapping of the cord have also been made recently, but exclusively with tumor surgery. We hereby present our experiences with dynamic mapping of the corticospinal tract (CST) in other types of spinal cord procedures that carry an increased risk of postoperative motor deficit, and thus could directly benefit from this technique. Two patients with intractable unilateral lower extremity pain due to metastatic disease of the sacrum and a thoraco-lumbar chordoma, respectively underwent thoracic cordotomy to interrupt the nociceptive pathways. A third patient with progressive leg weakness underwent cord untethering and surgical repair of a large thoracic myelomeningocele. In all three cases, multimodality intraoperative neurophysiologic testing included somatosensory and motor evoked potentials monitoring as well as dynamic mapping of the CST. CST mapping allowed safe advancement of the cordotomy probe and exploration of the meningocele sac with untethering of the anterior-lateral aspect of the cord respectively, resulting in postoperative preservation or improvement of motor strength from the pre-operative baseline. Stimulus thresholds varied likely with the distance between the stimulating probe and the CST as well as with the baseline motor strength in the mapped myotomes. [ABSTRACT FROM AUTHOR]

Surgery to the nervous system poses risks to neural structures be that mechanical, haemodynamical, chemical or thermal. The role of intraoperative neurophysiological monitoring (IONM) is to facilitate the assessment of the functional integrity of neural structures and provide a real time alerting system when changes caused by surgically induced insults are detected, with the goal of reducing the risk of postoperative neurological deficits. Furthermore, it is also used as a guidance system to map eloquent areas within the cortex and to identify specific neuronal structures, particularly when landmarks cannot be easily recognized. In this article, we focus on the various neurophysiological modalities used in intraoperative monitoring, their basic principles, indications and the information that they provide. We also examine the anaesthetic considerations and the checklist for the multidisciplinary team should an intraoperative alert be issued. [ABSTRACT FROM AUTHOR]

Fluorescein-guided surgery of high-grade gliomas (HGGs) increases the extent of tumor resection but its efficacy has been questioned, especially for tumors located close to functional networks. In these cases, navigated transcranial magnetic stimulation (nTMS) may be used to plan and guide a safe resection. The aim of this study was to assess the impact of these techniques combined with intraoperative neurophysiologic mapping (IONM) to achieve the maximal safe resection of tumors located in the motor area. We collected data of patients operated using a multimodal combination of sodium fluorescein–guided resection, nTMS motor planning, and IONM for HGGs in the motor area. The nTMS planning accuracy, extent of resection, and postoperative motor and functional status were compared with a matched control group of patients with HGG operated on only by IONM-guided resection. Forty-one patients treated by multimodal approach (group A) and 41 controls (group B) were included. The nTMS-based planning reliably identified the tumor/motor pathway spatial relationship (accuracy, 92.68%). We obtained in group A versus controls a higher gross total resection rate (73.17% vs. 51.22%; P = 0.04), and a reduction of cases with new permanent motor deficits (9.75% vs. 29.27%; P = 0.04) or Karnofsky Performance Status worsening (12.19% vs. 31.71%; P = 0.03). This study supports the role of the combination of sodium fluorescein–guided resection and nTMS-based planning for surgery of HGGs close to the motor pathway. This multimodal approach in combination with IONM may lead to customized preoperative planning, increased extent of resection, and improved functional outcome, compared with standard IONM-guided surgery. [ABSTRACT FROM AUTHOR]

Hemispherectomy is a successful and well-described treatment option for pediatric patients with hemispheric ictal onset, but adult outcomes have been far less studied. We describe the outcomes in adult patients with medically refractory epilepsy and hemispheric disease and the relationship to cerebral peduncle volume. We retrospectively reviewed adult hemispherectomy patients at our institution from 2015 to 2018. Patient data including demographic information, pathologic changes, seizure-free outcomes, and ipsilateral (i.e., surgical side) and contralateral (i.e., functional side) cerebral peduncle volume data were collected. We identified 4 adult patients who underwent hemispherectomy. The mean age at surgery was roughly 25 years. All patients were categorized as Engel I or II, and motor scores at last follow-up were unchanged. The mean volume for contralateral and ipsilateral cerebral peduncle means were 1.42 and 0.78 cm3, respectively (P = 0.01). These findings suggest that smaller ipsilateral cerebral peduncle size could potentially be associated with unchanged postoperative hemiparesis. We hypothesize that smaller ipsilateral peduncle size could have represented corticospinal tract reorganization in childhood, implying that the removed brain matter was mostly noncontributory to contralateral motor function. [ABSTRACT FROM AUTHOR]

Introduction: The pathophysiologic mechanism of paroxysmal kinesigenic dyskinesia (PKD) is largely unclear. Basal ganglia-thalamo-cortical circuit involvement is thought to underlie PKD pathophysiology. However, microstructural alternations in the motor circuit of PKD require further elucidation.Methods: Diffusion tensor imaging and high-resolution T1-weighted imaging were performed on 30 PKD patients (15 PRRT2 carriers, 15 PRRT2 non-carriers) and 15 matched healthy controls. Tract-based spatial statistics were conducted on diffusion indices to examine microstructural integrity of white matter. Voxel-based morphometry analysis was used to examine volumetric changes of gray matter. Multiple regression was employed to test the contribution of demography, disease duration, and PRRT2 status to pathological changes in brain structure.Results: Six (including two novel) PRRT2 mutations were identified in PKD patients who exhibited significantly reduced mean diffusivity mainly along the left corticospinal tract, and reduced gray matter volume in pre-supplementary motor area (preSMA) and right opercular part of inferior frontal gyrus (IFGoperc), compared to healthy controls. Both gray matter volume reductions in preSMA and diffusion indices of abnormal white matter negatively correlated with disease duration. Genotype-phenotype analysis revealed that PRRT2 mutation carriers had earlier onset age, longer attacks, and a larger proportion of bilateral symptoms than non-carriers.Conclusions: We observed that PRRT2 mutations were associated with disease severity, while neuroanatomical abnormality was associated with disease duration in patients with PKD. Aberrant microstructural changes in preSMA and IFG areas, independent of mutation status, point to dysregulated motor inhibition in patients and provide new insights into neurobiological mechanisms underlying motor symptoms of PKD. [ABSTRACT FROM AUTHOR]

Highlights • Adult Sema6A knockout mice have corticospinal tract (CST) defects. • The aberrant trajectories were evaluated by 3D reconstruction of PKC γ -stained fibers. • The CST defects in Sema6A knockout mice were highly complex and variable. • 3D reconstruction is a powerful method to visualize these CST axon guidance defects. Abstract The corticospinal tract (CST) has a complex and long trajectory that originates in the cerebral cortex and ends in the spinal cord. Semaphorin 6A (Sema6A), a member of the semaphorin family, is an important regulator of CST axon guidance. Previous studies have shown that postnatal Sema6A mutant mice have CST defects at the midbrain – hindbrain boundary and medulla. However, the routes the aberrant fibers take throughout the Sema6A mutant brain remain unknown. In this study, we performed 3D reconstruction of immunostained CST fibers to reevaluate the details of the abnormal CST trajectories in the brains of adult Sema6A mutant mice. Our results showed that the axon guidance defects reported in early postnatal mutants were consistently observed in adulthood. Those abnormal trajectories revealed by 3D analysis of brain sections were, however, more complex and variable than previously thought. In addition, 3D analysis allowed us to identify a few new patterns of aberrant projections. First, a subset of fibers that separated from and descended in parallel to the main bundle projected laterally at the caudal pons, subsequently changed direction by turning caudally, and extended to the medulla. Second, some abnormal fibers returned to the correct trajectory after deviating substantially from the original tract. Third, some fibers reached the pyramidal decussation normally but did not enter the dorsal funiculus. Section immunostaining combined with 3D reconstruction is a powerful method to track long projection fibers and to examine the entire nerve tracts of both normal and abnormal animals. [ABSTRACT FROM AUTHOR]

Summary Objectives In this longitudinal pilot study, we investigated how manual dexterity recovery was related to corticospinal tract (CST) injury and excitability, in six patients undergoing conventional rehabilitation. Methods Key components of manual dexterity, namely finger force control, finger tapping rate and independence of finger movements, were quantified. Structural MRI was obtained to calculate CST lesion load. CST excitability was assessed by measuring rest motor threshold (RMT) and the amplitude of motor evoked potentials (MEPs) using transcranial magnetic stimulation (TMS). Measurements were obtained at two weeks, three and six months post-stroke. Results At six months post-stroke, complete recovery of hand gross motor impairment (i.e., maximal Fugl-Meyer score for hand) had occurred in three patients and four patients had recovered ability to accurately control finger force. However, tapping rate and independence of finger movements remained impaired in all six patients at six months. Recovery in hand gross motor impairment and finger force control occurred in patients with smaller CST lesion load and almost complete recovery of CST excitability, although RMT or MEP size remained slightly altered in the stroke-affected hemisphere compared to the unaffected hemisphere. The two patients with poorest recovery showed persistent absence of MEPs and greatest structural injury to CST. Discussion The findings support good motor recovery being overall correlated with smaller CST lesion, and with almost complete recovery of CST excitability. However, impairment of manual dexterity persisted despite recovery in gross hand movements and grasping abilities, suggesting involvement of additional brain structures for fine manual tasks. [ABSTRACT FROM AUTHOR]

Highlights • Exercise was able to reverse the hyperactivity after the neonatal hypoxia-ischemia. • The acrobatic training decreased brain atrophy caused by neonatal hypoxia-ischemia. • The acrobatic exercise caused locomotion improvement after the hypoxia-ischemia. • Neonatal hypoxia-ischemia did not impact on morphology in motor control structures. Abstract The aim of this study was to evaluated motor function and morphological aspects of the components involved in motor control (sensorimotor cortex, spinal cord, sciatic nerve, neuromuscular junctions and skeletal muscle) in male Wistar rats exposed to a model of neonatal hypoxic-ischemic encephalopathy (HIE) and the possible influence of different physical exercise protocols – treadmill and acrobatic. Male Wistar rats at the 7th post-natal day (PND) were submitted to the HIE model and from the 22nd until 60th PND the exercise protocols (treadmill or acrobatic training) were running. After the training, the animals were evaluated in Open Field, Ladder Rung Walking and Rotarod tasks and after samples of the motor control components were collected. Our results evidenced that the acrobatic training reversed the hyperactivity and anxiety, caused locomotion improvement and decreased brain atrophy in HIE animals. We did not find morphological differences on sensorimotor cortex, spinal cord, sciatic nerve, neuromuscular junctions and skeletal muscle in the animals submitted to HIE model. These intriguing data support the statement of the Rice-Vannucci model does not seem to reproduce, in structures involved in control function, the damage found in humans that suffer HIE. Regarding the protocols of exercise, we proposed that the acrobatic exercise could be a good therapeutic option especially in children affected by neonatal HIE and can be responsible for good results in cognitive and motor aspects. [ABSTRACT FROM AUTHOR]

Highlights • Integrity of the corticospinal tract is associated with knee flexion strength in MS. • Diffusivity in the corticospinal tract is related to knee extension strength in MS. • CST integrity may be considered an outcome and/or predictor of strength adaptations. Abstract Muscle weakness, particularly in the lower-extremities, is common in multiple sclerosis (MS) and seemingly results from damage along white matter pathways in the central nervous system including the corticospinal tract (CST). This study examined CST structural integrity indicated by diffusion tensor imaging (DTI) related metrics (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], and axial diffusivity [AD]) as correlates of knee flexor (KF) and knee extensor (KE) muscle strength in MS. We included 36 persons with MS who underwent MRI and measurements of peak KE and KF strength using an isokinetic dynamometer. We examined associations using bivariate Spearman (r s) and partial Spearman correlation (pr s) analyses controlling for age and sex. Peak KF strength was significantly associated with FA (r s = 0.42) and RD (r s = −0.36) and peak KE strength was significantly associated with MD (r s = −0.47) and RD (r s = −0.36). The correlations were attenuated after controlling for age and sex, but the relationship between KF strength and FA demonstrated a trend towards significance (pr s = 0.33, p = 0.056). We provide evidence that the anatomical integrity of the CST may be associated with lower-extremity strength in MS. The attenuated correlations when controlling for age and sex suggest these factors, rather than MS per se, may be important contributors toward an association between CST DTI-metrics and KF and KE strength. Future rehabilitation trials of resistance training should consider including CST integrity as an outcome and/or predictor of strength adaptations. [ABSTRACT FROM AUTHOR]

Abstract Botulinum neurotoxin A (BTX-A) intervention has long-term benefits for children with obstetric brachial plexus palsy (OBPP). Although cortical plasticity has been widely studied, plasticity in white matter has not received as much attention. Here, six children with OBPP underwent functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) before and 6 months after BTX-A treatment. Surface electromyography (EMG) was recorded. The aim was to investigate changes in the corticospinal tract (CST) as an example longitudinal observation of white matter plasticity. Deterministic fiber tracking with a Fiber Assignment by Continuous Tracking algorithm was used to reconstruct the CST. Fiber tracts passing through a region of interest (ROI) in the posterior limb of the internal capsule and a target ROI in the upper-limb representation of M1 (defined by task-related fMRI) were selected as the CST. Motor performances were improved while EMG showed no significant difference 6 months after the treatment. We observed a significant increase in mean fractional anisotropy and a significant decrease in fiber number after treatment. We analyzed the correlations between DTI metrics and clinical motor assessments. Although the correlation results were not statistically significant, they support the notion that BTX-A treatment causes white matter plasticity and has a positive long-term outcome. Peripheral deafferentation may lead to altered information flow, resulting in the positive adaptation of white matter. This study provides novel insight into cerebral plasticity following peripheral nerve regeneration and indicates that a combination of relatively non-invasive therapies can accelerate plasticity of sensorimotor circuits and promote functional recovery in OBPP. Highlights • FA increased and fiber number decreased significantly after BTX-A treatment. • FA/fiber number tended to increase/decrease with motor function performance. • CST integrity might play a role in the motor rehabilitation of OBPP. • Non-invasive therapy might speed up plasticity and promote functional recovery. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine alteration of corticospinal tract in patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor tractograhy (DTT) focusing on the cervical spinal cord (C5) and transcranial magnetic stimulation (TMS). We recruited 38 ALS, 6 spinal and bulbar muscular atrophy (SBMA), 7 spastic paraplegia (SP) patients, and 8 age-matched normal controls, and then ALS were divided into two subgroups according to their clinical type: 28 ALS-limb and 10 ALS-bulbar. DTT was performed using the diffusion tensor image (DTI) track module to reconstruct two fiber tracts via C5. The fractional anisotropy (FA) values of ALS-total and ALS-limb patients were significantly reduced compared with normal controls, and SBMA patients. On the other hand, the mean diffusivity (MD) values were not significantly different among normal controls and the three disease groups. The rate of disease progression (ΔFRS-R) of ALS patients was significantly correlated with FA values and central motor conduction time (CMCT). In conclusion, the present study demonstrated a significant reduction of FA values in ALS patients, and the ΔFRS-R of ALS patients showed distinct regressions with FA values and CMCT, suggesting that this DTT analysis could be useful for detecting disease progression of ALS patients. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a valuable technique to assess and modulate human brain function in normal and pathological conditions. This critical review surveys the contributions of TMS to the diagnosis, insight into pathophysiology and treatment of genetically confirmed hereditary ataxias, a heterogeneous group of neurodegenerative disorders that can affect motor cortex and the corticospinal tract. Most studies were conducted on small sample sizes and focused on diagnostic approaches. The available data demonstrate early involvement of the corticospinal tract and motor cortex circuitry, and support the possible efficacy of cerebellar repetitive TMS (rTMS) as therapeutic approach. Further TMS-based studies are warranted, to establish biomarkers for early diagnosis and disease monitoring, explore the involvement of the cerebello-dentato-thalamo-cortical projection, study the effects of rTMS-induced plasticity, and utilize rTMS for treatment. [ABSTRACT FROM AUTHOR]

Background Different diffusion tensor imaging (DTI) has been used to estimate corticospinal tract (CST) structure in the context of stroke rehabilitation research. However, there is no gold standard for the estimate of CST structure in chronic stroke survivors. This study aims to determine the most accurate DTI-derived CST estimate that is associated with a clinical motor outcome measure. Methods We obtained imaging and behavioral data from a phase-I stroke rehabilitation clinical trial. We included thirty-seven chronic stroke survivors with mild­to­moderate motor impairment. Imaging data were processed using BrainSuite16a software. We calculated mean FA for each of 7 different ROIs/VOIs that include manually drawn 2-D ROIs and 3-D VOIs of CST from individual tractography or standard atlas. We compared ipsi- and contralesional CST FA for each method. Partial correlation was conducted between each CST FA asymmetry index and a time-based motor outcome measure, controlling for age and chronicity. Results Ipsilesional CST FA was significantly lower than contralesional CST FA for each of the 7 methods Only CST FA asymmetry from the 3-D individual CST tractography showed a significant correlation with the primary motor outcome (r = 0.46, p = .005), while CST FA from the other six methods did not. Comparison with existing methods Compared to the six other methods, CST FA asymmetry from 3-D individual tractography is the most accurate estimate of CST structure in this cohort of stroke survivors. Conclusion We recommend this method for future research seeking to understand brain-behavior mechanisms of motor recovery in chronic stroke survivors. [ABSTRACT FROM AUTHOR]

Background Motor imagery and actual movements share overlapping activation of brain areas but little is known about task-specific activation of distinct motor pathways during mental simulation of movements. For real contractions, it was demonstrated that the slow(er) motor pathways are activated differently in ballistic compared to tonic contractions but it is unknown if this also holds true for imagined contractions. Objective The aim of the present study was to assess the activity of fast and slow(er) motor pathways during mentally simulated movements of ballistic and tonic contractions. Methods H-reflexes were conditioned with transcranial magnetic stimulation at different interstimulus intervals to assess the excitability of fast and slow(er) motor pathways during a) the execution of tonic and ballistic contractions, b) motor imagery of these contraction types, and c) at rest. Results In contrast to the fast motor pathways, the slow(er) pathways displayed a task-specific activation: for imagined ballistic as well as real ballistic contractions, the activation was reduced compared to rest whereas enhanced activation was found for imagined tonic and real tonic contractions. Conclusions This study provides evidence that the excitability of fast and slow(er) motor pathways during motor imagery resembles the activation pattern observed during real contractions. The findings indicate that motor imagery results in task- and pathway-specific subliminal activation of distinct subsets of neurons in the primary motor cortex. [ABSTRACT FROM AUTHOR]

Objective Corticospinal tract (CST) dysfunction is common in the pre-ataxic stage of spinocerebellar ataxia type 2 (SCA2) but quantitative assessment of its progression over time has not been explored. The aim of this study was to quantify the progression of CST dysfunction in pre-ataxic SCA2 using transcranial magnetic stimulation (TMS). Methods Thirty-three pre-ataxic SCA2 mutation carriers and a 33 age- and gender-matched healthy controls were tested at baseline and 2-years follow-up by standardized clinical exams, validated clinical scales, and TMS. Results Pre-ataxic SCA2 mutation carriers showed a significant increase of resting motor thresholds (RMT) to abductor pollicis brevis (APB) and tibialis anterior (TA) muscles, and of central motor conduction time (CMCT) to TA at 2-years follow-up, over and above changes in healthy controls. The changes in the pre-ataxic SCA2 mutation carriers were independent of the presence of clinical signs of CST dysfunction at baseline, and independent of conversion to clinically definite SCA2 at 2-years follow-up. Conclusions TMS markers of CST dysfunction progress significantly during the pre-ataxic stage of SCA2. Significance TMS measures of CST dysfunction may provide biomarkers of disease progression prior to clinical disease expression that have potential utility for monitoring neuroprotective therapies in future clinical trials. [ABSTRACT FROM AUTHOR]

Objective A comprehensive treatment of Hereditary Spastic Paraplegia (HSP) should consider the specific pathophysiological changes in the spinal cord. Here we reported a detailed characterization of the spinal motoneuronal output in HSP during locomotion. Methods We recorded kinematics and electromyographic (EMG) activity of 12 leg muscles in 29 patients with pure forms of HSP and compared them with 30 controls while walking at matched speeds. We assessed the spinal locomotor output by evaluating EMG patterns and by mapping them onto the rostrocaudal location of the spinal motoneuron pools. Results The activity profiles of muscles innervated from the sacral segments were significantly wider in patients. Similarly, spinal maps revealed a tendency for spreading the main loci of activation, involving initially the sacral segments and, at more severe stages, the lumbar segments. Conclusions The degeneration of the corticospinal tract in HSP is associated with a widening of spinal locomotor output spreading from caudal to rostral segments. Significance The findings highlight pathophysiologically relevant differential changes in the spinal locomotor output in HSP related to the specific innervation of muscles in the spinal cord, and might be helpful for developing future therapeutic strategies and identifying physiological markers of the disease. [ABSTRACT FROM AUTHOR]

Motor disorders in patients with diabetes are associated with diabetic peripheral neuropathy, which can lead to symptoms such as lower extremity weakness. However, it is unclear whether central motor system disorders can disrupt motor function in patients with diabetes. In a streptozotocin-induced rat model of type 1 diabetes, we used intracortical microstimulation to evaluate motor representations in the motor cortex, recorded antidromic motor cortex responses to spinal cord stimulation to evaluate the function of corticospinal tract (CST) axons, and used retrograde labeling to evaluate morphological alterations of CST neurons. The diabetic rats exhibited size reductions in the hindlimb area at 4 weeks and in trunk and forelimb areas after 13 weeks, with the hindlimb and trunk area reductions being the most severe. Other areas were unaffected. Additionally, we observed reduced antidromic responses in CST neurons with axons projecting to lumbar spinal segments (CST-L) but not in those with axons projecting to cervical segments (CST-C). This was consistent with the observation that retrograde-labeled CST-L neurons were decreased in number following tracer injection into the spinal cord in diabetic animals but that CST-C neurons were preserved. These results show that diabetes disrupts the CST system components controlling hindlimb and trunk movement. This disruption may contribute to lower extremity weakness in patients. [ABSTRACT FROM AUTHOR]

The continuum hypothesis linking the behavioral variant of frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis (ALS) is supported by clinical, pathological, genetic, and neuroimaging evidence. In the present multimodal magnetic resonance study, we characterized the site and extent of shared neurostructural changes in gray and white matter in 20 bvFTD and 19 ALS patients without dementia. We found an overlap of macrostructural and microstructural damage in both patient groups compared with healthy controls, involving the right orbital and the bilateral anterior cingulate cortices, the corticospinal tract and corpus callosum. The quantification of gray and white matter damage within the areas of shared alterations highlighted a higher degree of atrophy in orbitofrontal and frontomedial regions in patients with more severe executive and/or behavioral symptoms, and a higher degree of degeneration in the motor pathway in patients with more severe motor neuron disorders. Our finding provides additional evidence confirming the FTD-ALS continuum hypothesis and supports the notion of a bimodal but convergent pattern of neurostructural changes characterizing bvFTD and ALS. [ABSTRACT FROM AUTHOR]

Objective Clinical data suggest early involvement of the corticospinal tract (CST) in spinocerebellar ataxia type 2 (SCA2). Here we tested if early CST degeneration can be detected in prodromal SCA2 mutation carriers by electrophysiological markers of CST integrity. Methods CST integrity was tested in 15 prodromal SCA2 mutation carriers, 19 SCA2 patients and 25 age-matched healthy controls, using corticomuscular (EEG-EMG) and intermuscular (EMG-EMG) coherence measures in upper and lower limb muscles. Results Significant reductions of EEG-EMG and EMG-EMG coherences were observed in the SCA2 patients, and to a similar extent in the prodromal SCA2 mutation carriers. In prodromal SCA2, EEG-EMG and EMG-EMG coherences correlated with the predicted time to ataxia onset. Conclusions Findings indicate early CST neurodegeneration in SCA2. EEG-EMG and EMG-EMG coherence may serve as biomarkers of early CST neurodegeneration in prodromal SCA2 mutation carriers. Significance Findings are important for developing preclinical disease markers in the context of currently emerging disease-modifying therapies of neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Damage to corticospinal fibers in the cervical spinal cord is known to impair dexterous hand movements. However, accumulating evidence has shown that precision grip can recover considerably through rehabilitative training. Recent multidisciplinary studies have revealed that, at the spinal level, this recovery is possible due to an indirect neural pathway through propriospinal neurons (PNs), which relay cortical commands to hand motoneurons. Although this indirect spinal pathway is heavily involved in recovery, its role is dwarfed by a simultaneous large-scale network reorganization spanning motor-related cortices and mesolimbic structures. This large-scale network reorganization is key to the regulation of recovery and future therapeutic strategies will need to take into account the involvement of these supraspinal centers in addition to the known role of the spinal cord. [ABSTRACT FROM AUTHOR]

Prenatal exposure to ethanol induces a relative increase in the numbers of pyramidal tract axons relative to the number of corticospinal projection neurons in somatosensory/motor cortices in the adult rat. The present study examines the effects of ethanol on the numbers of axons in the developing caudal pyramidal tract, i.e., corticospinal axons. Electron microscopic analyses of the pyramidal tracts of the offspring of pregnant rat dams fed a control diet ad libitum , pair-fed a liquid control diet, or fed an ethanol-containing diet ad libitum were performed. The pups were 5-, 15-, 30- and 90-days-old. The numbers of axons in control rats fell precipitously after postnatal day (P) 15 and the frequency of myelinated axons rose dramatically between P15 and P90. Ethanol exposure had no significant effect on the numbers of pyramidal tract axons at any age. Moreover, no ethanol-induced differences in the numbers of axons in different stages of myelination, i.e., axons that were “free” of glial associations, glia-engulfed, invested by 1–2 layers of myelin, or myelinated by 3+ layers of myelin, were detected on P15. Thus, it appears that (a) pyramidal tract axons are lost or pruned during the first two postnatal weeks and (b) postnatal development of pyramidal tract axons (e.g., pruning and myelination) is not affected by ethanol. The implications are that the ethanol-induced increase in the number of axons relative to the number of somata of corticospinal neurons detected in pups and adults results from the effects of ethanol on early stages (initiation) of axogenesis. [ABSTRACT FROM AUTHOR]

Objectives We investigated differences in recovery course of motor weakness according to the state of the corticospinal tract (CST) in putaminal hemorrhage, using diffusion tensor tractography (DTT). Methods We recruited 36 patients with complete weakness of the affected extremities at onset. The patients were classified into two groups according to the findings of DTT for the CST at chronic stage: group A- preserved integrity of the CST around the lesion, and group B- discontinued integrity of the CST. Motor function of the affected extremities was measured over a six month period using the Motricity Index (MI). Results The MI scores differed significantly each month, except at the onset, between group A and group B ( p < 0.05). In both groups, we observed significant increases between onset and one month, between one month and two months, between two month and three months, and between three months and four months ( p < 0 .05). However, there were no significant increases after four months ( p > 0 .05). The degree of difference between months was as follows: onset ∼1 month, 1 month ∼2 months, 2 months ∼3 months, and 3 months ∼4 months. Conclusions Patients with preserved integrity of the CST showed better motor function than patients with discontinued integrity of the CST. In both groups, significant motor recovery was achieved during the first four months after onset. In addition, the most rapid motor recovery occurred during the first month and then decreased gradually with the passage of time. [ABSTRACT FROM AUTHOR]

Background Preservation of function is essential in surgical resection of lesions involving the motor pathways. The aim of this work is to evaluate the effect of anatomic features of lesions located in the motor pathway on neurologic and functional outcome. We propose an evaluation score to assess the risk of postoperative worsening. Methods A total of 92 patients suffering from lesions involving the motor pathways have been studied for what concerns motor functions (muscular strength scale [MRC]) after surgical treatment. Patient-related, surgery-related, and lesion-related data were recorded to identify relations with motor outcomes. Cortical surfacing of the lesion and amount of millimeters of interface between the lesion and corticospinal tract have been investigated with preoperative magnetic resonance imaging sequences and tractographic reconstructions. Results Means of the MRC Scale preoperative and 7 days postoperative were 3.6 ± 2.23 and 3.8 ± 2.28 for the upper limbs, and 4.1 ± 2.31 and 4.4 ± 2.33 for the lower limbs, respectively. Patients that were stable or improved at 7 days from surgery were 82.6%. The anatomic features investigated have been summed up in a single score (envelopment/surfacing [ES]). In cases of ES classes V and VI, a total cumulative predicted worsening rate was 24.2% and 14.8%, respectively. The risk of worsening was 1.682 times greater for the higher ES classes (IV–VI). Conclusions The anatomic features of lesions are crucial in the prediction of motor outcome. The new proposed score (ES score) is useful to stratify motor function prognosis. [ABSTRACT FROM AUTHOR]

Background Involvement of the corticospinal tracts after perinatal arterial ischemic stroke (PAIS) is strongly correlated with adverse motor outcome. Methods Two full-term infants with PAIS, with two early MRI scans available, are reported. Results Diffusion weighted imaging (DWI)-MRI, performed within 24 h following onset of seizures and repeated 48 h later, clearly showed restricted diffusion within the middle cerebral artery territory on both MRIs, but clear patterns of signal intensity changes in the descending corticospinal tracts on the second MRI only. Conclusion Since involvement of the corticospinal tracts is essential for prediction of motor outcome, we may need to reconsider optimal timing of MR imaging for prediction of neurodevelopmental outcome after PAIS. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) researchers have predominately utilized rodents for SCI modeling and experimentation. Unfortunately, a large number of novel therapies developed in rodent models have failed to demonstrate efficacy in human clinical trials which suggests that improved animal models are an important translational tool. Recently, porcine models of SCI have been identified as a valuable intermediary model for preclinical evaluation of promising therapies to aid clinical translation. However, the localization of the major spinal tracts in pigs has not yet been described. Given that significant differences exist in the location of the corticospinal tract (CST) between rodents and humans, determining its location in pigs will provide important information related to the translational potential of the porcine pre-clinical model of SCI. Thus, the goal of this study is to investigate the localization of the CST within the porcine spinal cord. Mature female domestic pigs (n = 4, 60 kg) received microinjections of fluorescent dextran tracers (Alexa Fluor, 10,000 MW) into the primary motor cortex, using image-guided navigation (StealthStation ® ), to label the CST. At 5 weeks post-tracer injection animals were euthanized, the entire neuroaxis harvested and processed for histological examination. Serial sections of the brain and spinal cord were prepared and imaged using confocal microscopy to observe the location of the CST in pigs. Results demonstrate that the CST of pigs is located in the lateral white matter, signifying greater similarity to human anatomical structure compared to that of rodents. We conclude that the corticospinal tract in pigs demonstrates anatomical similarity to human, suggesting that the porcine model has importance as a translational intermediary pre-clinical model. [ABSTRACT FROM AUTHOR]

Objective The detection of upper motor neuron (UMN) dysfunction is necessary for the diagnosis of amyotrophic lateral sclerosis (ALS). However, signs of UMN dysfunction may be difficult to establish. This study aimed to determine whether motor-evoked potential (MEP) gain (MEP area/background electromyographic activity) represents an efficient alternative to assess UMN dysfunction. Methods MEP area, MEP/compound muscle action potential (CMAP) area ratio, and MEP gain were tested at different force levels in healthy control subjects and ALS patients. Receiver operating characteristic (ROC) curve analyses was used to determine the diagnostic utility of MEP gain and compare it to alternative techniques, namely, diffusion tensor imaging (DTI) and the triple stimulation technique (TST). Results MEP gain revealed a significant difference between the patients and healthy control subjects in contrast to MEP area and MEP/CMAP area ratio. The diagnostic utility of MEP gain was comparable with that of TST and superior to that of DTI. Conclusion MEP gain can distinguish ALS patients from control subjects and may be helpful for the diagnosis of ALS. Significance MEP gain appears to be a useful adjunct test and noninvasive method for the assessment of corticospinal dysfunction. [ABSTRACT FROM AUTHOR]

An implanted neurotrophin-3 (NT3)-chitosan scaffold can recruit endogenous neural stem cells to migrate to a lesion region and differentiate into mature neurons after adult spinal cord injury (SCI). However, the identities of these newborn neurons and whether they can form functional synapses and circuits to promote recovery after paraplegia remain unknown. By using combined advanced technologies, we revealed here that the newborn neurons of several subtypes received synaptic input from the corticospinal tract (CST), rubrospinal tract (RST), and supraspinal tracts. They formed a functional neural circuit at the injured spinal region, further driving the local circuits beneath the lesion. Our results showed that the NT3-chitosan scaffold facilitated the maturation of spinal neurons and the reestablishment of the spinal neural circuit in the lesion region 12 weeks after SCI. Transsynaptic virus experiments revealed that these newborn spinal neurons received synaptic connections from the CST and RST and drove the neural circuit beneath the lesion via newly formed synapses. These re-established circuits successfully recovered the formation and function of the neuromuscular junction (NMJ) beneath the lesion spinal segments. These findings suggest that the NT3-chitosan scaffold promotes the formation of relay neural circuits to accommodate various types of brain descending inputs and facilitate functional recovery after paraplegia. [Display omitted] • The newborn neurons could be classified into several subtypes that possessed normal spinal cord neuronal characteristics. • Corticospinal tract and rubrospinal tract to reenter the lesion area, where they came in close contact with newborn neurons. • The trans-newborn neuron monosynaptic input neural circuit was reconstructed. • The brain-spinal cord neural network was reestablished. • Local circuits beneath the lesion were reformed, and NMJ morphology and function of anterior tibialis were improved. [ABSTRACT FROM AUTHOR]

Motor map reorganization is believed to be one mechanism underlying rehabilitation-induced functional recovery. Although the ipsilesional secondary motor area has been known to reorganize motor maps and contribute to rehabilitation-induced functional recovery, it is unknown how the secondary motor area is reorganized by rehabilitative training. In the present study, using skilled forelimb reaching tasks, we investigated neural network remodeling in the rat rostral forelimb area (RFA) of the secondary motor area during 4 weeks of rehabilitative training. Following photothrombotic stroke in the caudal forelimb area (CFA), rehabilitative training led to task-specific recovery and motor map reorganization in the RFA. A second injury to the RFA resulted in reappearance of motor deficits. Further, when both the CFA and RFA were destroyed simultaneously, rehabilitative training no longer improved task-specific recovery. In neural tracer studies, although rehabilitative training did not alter neural projection to the RFA from other brain areas, rehabilitative training increased neural projection from the RFA to the lower spinal cord, which innervates the muscles in the forelimb. Double retrograde tracer studies revealed that rehabilitative training increased the neurons projecting from the RFA to both the upper cervical cord, which innervates the muscles in the neck, trunk, and part of the proximal forelimb, and the lower cervical cord. These results suggest that neurons projecting to the upper cervical cord provide new connections to the denervated forelimb area of the spinal cord, and these new connections may contribute to rehabilitation-induced task-specific recovery and motor map reorganization in the secondary motor area. [ABSTRACT FROM AUTHOR]

Lesions to the corticospinal tract result in several neurological symptoms and several rehabilitation protocols have proven useful in attempts to direct underlying plastic phenomena. However, the effects that such protocols may exert on the dendritic spines of motoneurons to enhance accuracy during rehabilitation are unknown. Thirty three female Sprague-Dawley adult rats were injected stereotaxically at the primary motor cerebral cortex (Fr1) with saline (CTL), or kainic acid (INJ), or kainic acid and further rehabilitation on a treadmill 16 days after lesion (INJ+RB). Motor performance was evaluated with the the Basso, Beatie and Bresnahan (BBB) locomotion scale and in the Rotarod. Spine density was quantified in a primary dendrite of motoneurons in Lamina IX in the ventral horn of the thoracolumbar spinal cord as well as spine morphology. AMPA, BDNF, PSD-95 and synaptophysin expression was evaluated by Western blot. INJ+RB group showed higher scores in motor performance. Animals from the INJ+RB group showed more thin, mushroom, stubby and wide spines than the CTL group, while the content of AMPA, BDNF, PSD-95 and Synaptophysin was not different between the groups INJ+RB and CTL. AMPA and synaptophysin content was greater in INJ group than in CTL and INJ+RB groups. The increase in the proportion of each type of spine observed in INJ+RB group suggest spinogenesis and a greater capability to integrate the afferent information to motoneurons under relatively stable molecular conditions at the synaptic level. • The lesion to the motor cortex caused impaired gait and motor coordination. • The rehabilitation in treadmill improved the motor performance. • Thin and mushroom spines increased in the injured and injured-andrehabilitated rats. • Stubby and wide spines increased in the injured-and-rehabilitated rats. • The proteins AMPA, BDNF and Synaptophysin increased in the injured rats. [ABSTRACT FROM AUTHOR]

Behavioral responsiveness and awareness levels correlate with the degree of functional connectivity within cortical-thalamocortical networks, whose breakdown accounts for chronic disorders of consciousness (DOC). Our study was aimed at assessing the role of the primary motor area (M1) and premotor-M1 circuitry dysfunction in motor output deterioration in minimally conscious state (MCS) and unresponsive wakefulness syndrome (UWS) patients. As a control group, we included a healthy subject (HC) sample in the study. We evaluated the effects of different types of transcranial magnetic stimuli over M1 by recording post-stimulus time histogram (PSTH), which includes a series of peaks of unit firing activity that match with D and I-waves, characterizing the descending corticospinal volleys evoked by transcranial magnetic stimuli. As compared to HC, DOC patients showed a dysfunction of intra-M1 and premotor-M1 circuits, which correlated with the Coma Recovery Scale-Revised scorings. Nonetheless, one UWS patient showed a partially preserved premotor-M1 circuitry, paralleled by a severe intra-M1 circuitry dysfunction. Our data suggest that motor unresponsiveness in some DOC patients may be due to a pure motor output failure, as in the functional locked-in syndrome (fLIS), rather than to a premotor-motor connectivity impairment, which instead characterizes MCS and UWS. [ABSTRACT FROM AUTHOR]

Objective To evaluate if the corticospinal tract is affected in the prodromal stage of spinocerebellar ataxia type 2 (SCA2), prior to development of the cerebellar syndrome. Methods A cross-sectional study was conducted in 37 non-ataxic SCA2 mutation carriers and in age- and sex-matched healthy controls. All subjects underwent clinical assessment and transcranial magnetic stimulation to determine corticospinal tract integrity to the right abductor pollicis brevis and tibialis anterior muscles. Results Non-ataxic SCA2 mutation carriers showed significantly higher resting and active motor thresholds for both muscles, and prolonged cortical silent periods and central motor conduction times (CMCT), compared to controls. CMCT to the tibialis anterior correlated directly with CAG repeat size, and inversely with predicted time to ataxia onset. Conclusion Findings provide novel electrophysiological evidence for affection of the corticospinal tract and motor cortex in prodromal SCA2. Slowed conduction in the corticospinal tract to the lower limbs reflects polyglutamine neurotoxicity, and predicts time to ataxia onset. Significance Identification of corticospinal tract damage and decreases motor cortical excitability in the prodromal stage of SCA2 allows early disease monitoring. This will become important as soon as effective neuroprotective treatment will be available. [ABSTRACT FROM AUTHOR]

Aims: To investigate the extent of white matter damage in children with unilateral cerebral palsy (UCP) caused by periventricular white matter lesions comparing between unilateral and bilateral lesions; and to investigate a relationship between white matter microstructure and hand function.Methods and Procedures: Diffusion MRI images from 46 children with UCP and 18 children with typical development (CTD) were included. Subjects were grouped by side of hemiparesis and unilateral or bilateral lesions. A voxel-wise white matter analysis was performed to identify regions where fractional anisotropy (FA) was significantly different between UCP groups and CTD; and where FA correlated with either dominant or impaired hand function (using Jebsen Taylor Hand Function Test).Outcomes and Results: Children with unilateral lesions had reduced FA in the corticospinal tract of the affected hemisphere. Children with bilateral lesions had widespread reduced FA extending into all lobes. In children with left hemiparesis, impaired hand function correlated with FA in the contralateral corticospinal tract. Dominant hand function correlated with FA in the posterior thalamic radiations as well as multiple other regions in both left and right hemiparesis groups.Conclusions and Implications: Periventricular white matter lesions consist of focal and diffuse components. Focal lesions may cause direct motor fibre insult resulting in motor impairment. Diffuse white matter injury is heterogeneous, and may contribute to more global dysfunction. [ABSTRACT FROM AUTHOR]

Previously we showed that expansion of intracerebral hemorrhage (ICH) into the internal capsule greatly aggravated neurological symptoms in mice. Here we examined ICH-associated events in the internal capsule with relation to neurological dysfunction. Corticospinal axons labeled by biotinylated dextran amine exhibited fragmented appearance after ICH induced by local injection of collagenase into the internal capsule. Fragmentation of axonal structures was confirmed by neurofilament-H immunostaining, which was evident from 6 h after induction of ICH. We also observed accumulation of amyloid precursor protein, which indicated compromised axonal transport, from 3 h after induction of ICH. The early defect in axonal transport was accompanied by a robust decline in motor performance. Local application of an axonal transport inhibitor colchicine to the internal capsule induced a prompt decline in motor performance, suggesting that compromised axonal transport is closely associated with early neurological dysfunction in ICH. Arrest of axonal transport and fragmentation of axonal structures were also induced by local injection of thrombin, but not by thrombin receptor activator peptide-6, a protease-activated receptor-1 agonist. These results suggest that receptor-independent actions of thrombin mediate disruption of structure and function of axons by hemorrhage expansion into the internal capsule, which leads to severe neurological dysfunction. [ABSTRACT FROM AUTHOR]

Objective The surgical treatment of cavernous malformations involving the posterior limb of the internal capsule (PLIC-CMs) is challenging. The aim of this study was to determine the utility and predictive value of preoperative diffusion tensor imaging (DTI) in the surgical treatment of PLIC-CMs. Methods Patients with PLIC-CMs who were surgically treated between September 2012 and June 2015 were reviewed. All patients underwent preoperative DTI. Three major fiber tracts were selected for evaluation: 1) corticospinal tract (CST); 2) arcuate fasciculus (AF); and 3) optic radiation (OR). The utility of preoperative DTI for surgical approach selection and intraoperative navigation was documented. An involvement grading system of the major fibers was applied to determine the predictive value of preoperative DTI. A last modified Rankin Scale (mRS) score of 0–2 was considered a good outcome, and a last mRS >2 was considered a poor outcome. Results Thirteen patients with 13 PLIC-CMs were reviewed in this study. All the lesions were radically resected via the corridor formed by CST, AF, and OR. None of the patents suffered from mRS >3, and 7 patients (53.8%) got good outcomes at the last clinic visit. The difference between the preoperative mRS scores and last mRS scores was not significant ( P = 0.673). The involvement grade of the fiber tracts was significantly associated with the surgical outcome ( P = 0.011). Conclusions Preoperative DTI may be a promising tool to determine the surgical approach and predict the surgical outcomes in patients with PLIC-CMs. [ABSTRACT FROM AUTHOR]

Purpose: To apply DTI to detect early extrapontine extension of pediatric diffuse intrinsic pontine glioma along the corticospinal tracts.Methods: In children with diffuse intrinsic pontine glioma, low-grade brainstem glioma, and age-matched controls, DTI metrics were measured in the posterior limb of the internal capsule and posterior centrum semiovale. Histological examination was available in one patient.Results: 6 diffuse intrinsic pontine glioma, 8 low-grade brainstem glioma, and two groups of 25 controls were included. In diffuse intrinsic pontine glioma compared to controls, fractional anisotropy was lower in the bilateral posterior limb of the internal capsule, axial diffusivity was lower in the bilateral posterior centrum semiovale and posterior limb of the internal capsule, while radial diffusivity was higher in the bilateral posterior limb of the internal capsule. No significant differences were found between low-grade brainstem glioma and controls. In diffuse intrinsic pontine glioma compared to low-grade brainstem glioma, axial diffusivity was lower in the bilateral posterior limb of the internal capsule. Histological examination in one child showed tumor cells in the posterior limb of the internal capsule.Conclusion: Reduction in fractional anisotropy and axial diffusivity and increase in radial diffusivity in diffuse intrinsic pontine glioma may reflect tumor extension along the corticospinal tracts as shown by histology. DTI may detect early extrapontine tumor extension in diffuse intrinsic pontine glioma before it becomes apparent on conventional MRI sequences. [ABSTRACT FROM AUTHOR]