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Journal of Neurology, Neurosurgery, and... Jan 2022To investigate sensitivity of brain MRI and neurological examination for detection of upper motor neuron (UMN) degeneration in patients with amyotrophic lateral...
OBJECTIVES
To investigate sensitivity of brain MRI and neurological examination for detection of upper motor neuron (UMN) degeneration in patients with amyotrophic lateral sclerosis (ALS).
METHODS
We studied 192 patients with ALS and 314 controls longitudinally. All patients visited our centre twice and underwent full neurological examination and brain MRI. At each visit, we assessed UMN degeneration by measuring motor cortex thickness (CT) and pyramidal tract fibre density (FD) corresponding to five body regions (bulbar region and limbs). For each body region, we measured degree of clinical UMN and lower motor neuron (LMN) symptom burden using a validated scoring system.
RESULTS
We found deterioration over time of CT of motor regions (p≤0.0081) and progression of UMN signs of bulbar region and left arm (p≤0.04). FD was discriminative between controls and patients with moderate/severe UMN signs (all regions, p≤0.034), but did not change longitudinally. Higher clinical UMN burden correlated with reduced CT, but not lower FD, for the bulbar region (p=2.2×10) and legs (p≤0.025). In the arms, we found that severe LMN signs may reduce the detectability of UMN signs (p≤0.043). With MRI, UMN degeneration was detectable before UMN signs became clinically evident (CT: p=1.1×10, FD: p=6.3×10). Motor CT, but not FD, deteriorated more than UMN signs during the study period.
CONCLUSIONS
Motor CT is a more sensitive measure of UMN degeneration than UMN signs. Motor CT and pyramidal tract FD are discriminative between patients and controls. Brain MRI can monitor UMN degeneration before signs become clinically evident. These findings promote MRI as a potential biomarker for UMN progression in clinical trials in ALS.
Topics: Amyotrophic Lateral Sclerosis; Biomarkers; Case-Control Studies; Female; Humans; Magnetic Resonance Imaging; Male; Motor Cortex; Motor Neurons; Netherlands; Neuroimaging; Neurologic Examination; Pyramidal Tracts
PubMed: 34663622
DOI: 10.1136/jnnp-2021-327269 -
Journal of Digital Imaging Apr 2022We investigate the correlation between diffusion tensor imaging (DTI)-derived metric statistics and motor strength grade of insular glioma patients after optimizing the...
Optimized Tractography Mapping and Quantitative Evaluation of Pyramidal Tracts for Surgical Resection of Insular Gliomas: a Correlative Study with Diffusion Tensor Imaging-Derived Metrics and Patient Motor Strength.
We investigate the correlation between diffusion tensor imaging (DTI)-derived metric statistics and motor strength grade of insular glioma patients after optimizing the pyramidal tract (PT) delineation. Motor strength grades of 45 insular glioma patients were assessed. All the patients underwent structural and diffusion MRI examination before and after surgery. We co-registered pre- and post-op datasets, and a two-tensor unscented Kalman filter (UKF) algorithm was employed to delineate bilateral PTs after DWI pre-processing. The tractography results were voxelized, and their labelmaps were cropped according to the location of frontal and insular parts of the lesion. Both the whole and cropped labelmaps were used as regions of interest to analyze fractional anisotropy (FA) and Trace statistics; hence, their ratios were calculated (lesional side tract/contralateral normal tract). The combination of DWI pre-processing and two-tensor UKF algorithm successfully delineated bilateral PTs of all the patients. It effectively accomplished both full fiber delineation within the edema and an extensive lateral fanning that had a favorable correspondence to the bilateral motor cortices. Before surgery, correlations were found between patients' motor strength grades and ratios of PT volume and FA standard deviation (SD). Nearly 3 months after surgery, correlations were found between motor strength grades and the ratios of metric statistics as follows: whole PT volume, whole mean FA, and FA SD. We substantiated the correlation between DTI-derived metric statistics and motor strength grades of insular glioma patients. Moreover, we posed a workflow for comprehensive pre- and post-op DTI quantitative research of glioma patients.
Topics: Benchmarking; Brain Neoplasms; Diffusion Tensor Imaging; Glioma; Humans; Pyramidal Tracts
PubMed: 35064370
DOI: 10.1007/s10278-021-00578-4 -
Frontiers in Neural Circuits 2019There exist two major types of striatum-targeting neocortical neurons, specifically, intratelencephalic (IT) neurons and pyramidal-tract (PT) neurons. Regarding their...
There exist two major types of striatum-targeting neocortical neurons, specifically, intratelencephalic (IT) neurons and pyramidal-tract (PT) neurons. Regarding their striatal projections, it was once suggested that IT axons are extended whereas PT axons are primarily focal. However, subsequent study with an increased number of well-stained extended axons concluded that such an apparent distinction was spurious due to limited sample size. Recent work using genetically labeled neurons reintroduced the differential spatial extent of the striatal projections of IT and PT neurons through population-level analyses, complemented by observations of single axons. However, quantitative IT vs. PT comparison of a large number of axons remained to be conducted. We analyzed the data of axonal end-points of 161 IT neurons and 33 PT neurons in the MouseLight database (http://ml-neuronbrowser.janelia.org/). The number of axonal end-points in the ipsilateral striatum exhibits roughly monotonically decreasing distributions in both neuron types. Excluding neurons with no ipsilateral end-point, the distributions of the logarithm of the number of ipsilateral end-points are considerably overlapped between IT and PT neurons, although the proportion of neurons having more than 50 ipsilateral end-points is somewhat larger in IT neurons than in PT neurons. Looking at more details, among IT subpopulations in the secondary motor area (MOs), layer 5 neurons and bilateral striatum-targeting layer 2/3 neurons, but not contralateral striatum-non-targeting layer 2/3 neurons, have a larger number of ipsilateral end-points than MOs PT neurons. We also found that IT ipsilateral striatal axonal end-points are on average more widely distributed than PT end-points, especially in the medial-lateral direction. These results indicate that IT and PT striatal axons differ in the frequencies and spatial extent of end-points while there are wide varieties within each neuron type.
Topics: Animals; Axons; Cell Shape; Corpus Striatum; Databases, Factual; Mice; Neurons; Pyramidal Tracts
PubMed: 31803027
DOI: 10.3389/fncir.2019.00071 -
Frontiers in Neural Circuits 2013Although transcranial magnetic stimulation (TMS) activates a number of different neuron types in the cortex, the final output elicited in corticospinal neurones is... (Review)
Review
Although transcranial magnetic stimulation (TMS) activates a number of different neuron types in the cortex, the final output elicited in corticospinal neurones is surprisingly stereotyped. A single TMS pulse evokes a series of descending corticospinal volleys that are separated from each other by about 1.5 ms (i.e., ~670 Hz). This evoked descending corticospinal activity can be directly recorded by an epidural electrode placed over the high cervical cord. The earliest wave is thought to originate from the direct activation of the axons of fast-conducting pyramidal tract neurones (PTN) and is therefore termed "D" wave. The later waves are thought to originate from indirect, trans-synaptic activation of PTNs and are termed "I" waves. The anatomical and computational characteristics of a canonical microcircuit model of cerebral cortex composed of layer II and III and layer V excitatory pyramidal cells, inhibitory interneurons, and cortico-cortical and thalamo-cortical inputs can account for the main characteristics of the corticospinal activity evoked by TMS including its regular and rhythmic nature, the stimulus intensity-dependence and its pharmacological modulation. In this review we summarize present knowledge of the physiological basis of the effects of TMS of the human motor cortex describing possible interactions between TMS and simple canonical microcircuits of neocortex. According to the canonical model, a TMS pulse induces strong depolarization of the excitatory cells in the superficial layers of the circuit. This leads to highly synchronized recruitment of clusters of excitatory neurons, including layer V PTNs, and of inhibitory interneurons producing a high frequency (~670 Hz) repetitive discharge of the corticospinal axons. The role of the inhibitory circuits is crucial to entrain the firing of the excitatory networks to produce a high-frequency discharge and to control the number and magnitude of evoked excitatory discharge in layer V PTNs. In summary, simple canonical microcircuits of neocortex can explain activation of corticospinal neurons in human motor cortex by TMS.
Topics: Animals; Humans; Motor Cortex; Nerve Net; Pyramidal Tracts; Transcranial Magnetic Stimulation
PubMed: 23407686
DOI: 10.3389/fncir.2013.00018 -
Experimental Neurology Nov 2019Spared corticospinal tract (CST) and proprioceptive afferent (PA) axons sprout after injury and contribute to rewiring spinal circuits, affecting motor recovery. Loss of...
Spared corticospinal tract (CST) and proprioceptive afferent (PA) axons sprout after injury and contribute to rewiring spinal circuits, affecting motor recovery. Loss of CST connections post-injury results in corticospinal signal loss and associated reduction in spinal activity. We investigated the role of activity loss and injury on CST and PA sprouting. To understand activity-dependence after injury, we compared CST and PA sprouting after motor cortex (MCX) inactivation, produced by chronic MCX muscimol microinfusion, with sprouting after a CST lesion produced by pyramidal tract section (PTx). Activity suppression, which does not produce a lesion, is sufficient to trigger CST axon outgrowth from the active side to cross the midline and to enter the inactivated side of the spinal cord, to the same extent as PTx. Activity loss was insufficient to drive significant CST gray matter axon elongation, an effect of PTx. Activity suppression triggered presynaptic site formation, but less than PTx. Activity loss triggered PA sprouting, as PTx. To understand injury-dependent sprouting further, we blocked microglial activation and associated inflammation after PTX by chronic minocycline administration after PTx. Minocycline inhibited myelin debris phagocytosis contralateral to PTx and abolished CST axon elongation, formation of presynaptic sites, and PA sprouting, but not CST axon outgrowth from the active side to cross the midline. Our findings suggest sprouting after injury has a strong activity dependence and that microglial activation after injury supports axonal elongation and presynaptic site formation. Combining spinal activity support and inflammation control is potentially more effective in promoting functional restoration than either alone.
Topics: Animals; Brain Injuries; Male; Microglia; Nerve Regeneration; Neurons; Neurons, Afferent; Pyramidal Tracts; Rats; Rats, Sprague-Dawley; Recovery of Function; Spinal Cord Injuries
PubMed: 31326353
DOI: 10.1016/j.expneurol.2019.113015 -
Acta Neuropathologica Communications Jan 2021Transactive response DNA-binding protein 43 kDa (TDP-43) has been identified as the major component of ubiquitinated inclusions found in patients with sporadic...
Transactive response DNA-binding protein 43 kDa (TDP-43) has been identified as the major component of ubiquitinated inclusions found in patients with sporadic amyotrophic lateral sclerosis (ALS). Increasing evidence suggests prion-like transmission of TDP-43 aggregates via neuroanatomic connection in vitro and pyramidal tract in vivo. However, it is still unknown whether the spreading of pathological TDP-43 sequentially via pyramidal tract can initiate ALS-like pathology and phenotypes. In this study, we reported that injection of TDP-43 preformed fibrils (PFFs) into the primary motor cortex (M1) of Thy1-e (IRES-TARDBP) 1 mice induced the spreading of pathological TDP-43 along pyramidal tract axons anterogradely. Moreover, TDP-43 PFFs-injected Thy1-e (IRES-TARDBP) 1 mice displayed ALS-like neuropathological features and symptoms, including motor dysfunctions and electrophysiological abnormalities. These findings provide direct evidence that transmission of pathological TDP-43 along pyramidal tract induces ALS-like phenotypes, which further suggest the potential mechanism for TDP-43 proteinopathy.
Topics: Amyotrophic Lateral Sclerosis; Animals; Axonal Transport; DNA-Binding Proteins; Humans; Mice; Mice, Transgenic; Motor Cortex; Protein Aggregates; Protein Aggregation, Pathological; Pyramidal Tracts
PubMed: 33461623
DOI: 10.1186/s40478-020-01112-3 -
Turkish Neurosurgery 2014To explore the clinical value of combining pyramidal tract mapping, microscopic-based neuronavigation, and intraoperative magnetic resonance imaging (iMRI) in the...
Combining pyramidal tract mapping, microscopic-based neuronavigation, and intraoperative magnetic resonance imaging improves outcome of epilepsy foci resection in the sensorimotor cortex.
AIM
To explore the clinical value of combining pyramidal tract mapping, microscopic-based neuronavigation, and intraoperative magnetic resonance imaging (iMRI) in the surgical treatment of epileptic foci involving sensorimotor cortex.
MATERIAL AND METHODS
We retrospectively analyzed 69 patients with focal epilepsy involving motor and sensory cortex. The surgical operations in Group I (n=38) were performed under the guidance of conventional neuronavigation, and the operations of Group II (n=31) were aided by combining pyramidal tract mapping, microscopic-based neuronavigation and the iMRI technique. Chi square test was used to compare seizure outcome and neurological deficits across groups.
RESULTS
7 patients (18.4%) in Group I, and 3 patients (9.7%) in Group II didn't recover to the level of preoperative strength within one year post-operation. The 2-year follow-up survey showed that more patients in Group II compared to Group I (71% vs. 55.3%, p=0.181) had a good outcome (Engel class I ~ II).
CONCLUSION
The techniques of combining pyramidal tract mapping, microscopic-based neuronavigation and iMRI aid in precise mapping and hence resection of epileptic foci in sensorimotor cortex, which lead to improvement of surgical efficacy and significant reduction of postoperative loss of function.
Topics: Adolescent; Adult; Diffusion Tensor Imaging; Epilepsy; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Monitoring, Intraoperative; Nervous System Diseases; Neuronavigation; Postoperative Complications; Pyramidal Tracts; Retrospective Studies; Sensorimotor Cortex; Treatment Outcome; Young Adult
PubMed: 25050679
DOI: 10.5137/1019-5149.JTN.9517-13.0 -
The Journal of Neuroscience : the... Sep 2019Reorganization of residual descending motor circuits underlies poststroke recovery. We previously clarified a causal relationship between the cortico-rubral tract and...
Reorganization of residual descending motor circuits underlies poststroke recovery. We previously clarified a causal relationship between the cortico-rubral tract and intensive limb use-induced functional recovery after internal capsule hemorrhage (ICH). However, other descending tracts, such as the cortico-reticular tract, might also be involved in rehabilitation-induced compensation. To investigate whether rehabilitation-induced recovery after ICH involves a shift in the compensatory circuit from the cortico-rubral tract to the cortico-reticular tract, we established loss of function of the cortico-rubral tract or/and cortico-reticular tract using two sets of viral vectors comprising the Tet-on system and designer receptors exclusively activated by the designer drug system. We used an ICH model that destroyed almost 60% of the corticofugal fibers. Anterograde tracing in rehabilitated rats revealed abundant sprouting of axons from the motor cortex in the red nucleus but not in the medullary reticular formation during the early phase of recovery. This primary contribution of the cortico-rubral tract was demonstrated by its selective blockade, whereas selective cortico-reticular tract silencing had little effect. Interestingly, cortico-rubral tract blockade from the start of rehabilitation induced an obvious increase of axon sprouting in the reticular formation with substantial functional recovery. Additional cortico-reticular tract silencing under the cortico-rubral tract blockade significantly worsened the recovered forelimb function. Furthermore, the alternative recruitment of the cortico-reticular tract was gradually induced by intensive limb use under cortico-rubral tract blockade, in which cortico-reticular tract silencing caused an apparent motor deficit. These findings indicate that individual cortico-brainstem pathways have dynamic compensatory potency to support rehabilitative functional recovery after ICH. This study aimed to clarify the interaction between the cortico-rubral and the cortico-reticular tract during intensive rehabilitation and functional recovery after capsular stroke. Pathway-selective disturbance by two sets of viral vectors revealed that the cortico-rubral tract was involved in rehabilitation-induced recovery of forelimb function from an early phase after internal capsule hemorrhage, but that the cortico-reticular tract was not. The sequential disturbance of both tracts revealed that the cortico-reticular tract was recruited and involved in rehabilitation-induced recovery when the cortico-rubral tract failed to function. Our data demonstrate a dynamic compensatory action of individual cortico-brainstem pathways for recovery through poststroke rehabilitation.
Topics: Animals; Brain Stem; Male; Motor Cortex; Neuroanatomical Tract-Tracing Techniques; Pyramidal Tracts; Rats; Rats, Wistar; Recovery of Function; Red Nucleus; Stroke
PubMed: 31395620
DOI: 10.1523/JNEUROSCI.0649-19.2019 -
Zhurnal Voprosy Neirokhirurgii Imeni N.... 2016Practical application of methods for intravital examination of the brain pathways, such as preoperative diffusion tensor imaging (DTI) tractography and intraoperative...
BACKGROUND
Practical application of methods for intravital examination of the brain pathways, such as preoperative diffusion tensor imaging (DTI) tractography and intraoperative neurophysiological monitoring, facilitates safer resection of intracranial tumors located near the pyramidal tracts (PTs).
PURPOSE
The study purpose was to investigate the relationships between intracerebral tumors of different histological nature and the pyramidal tract based on preoperative DTI tractography and various methods of intraoperative neurophysiological monitoring for intraoperative identification of the pyramidal tract, depending on different variants of the topographo-anatomic relationships between the pyramidal fascicle and the tumor.
MATERIAL AND METHODS
The study included 29 patients with supratentorial tumors of a different histological structure. Of these, 2 patients had grade I tumors, 8 patients had grade II tumors, 4 patients had grade III tumors, 11 patients grade IV tumors, and 4 patients had brain metastases. The patients underwent preoperative DTI tractography with PT reconstruction and evaluation of the topographo-anatomic relationships between the pyramidal tract and the tumor (tract: intact, infiltrated, displaced). Neurophysiological monitoring (direct electrical stimulation in 24 patients and transcranial motor evoked potentials in 26 patients) was used during surgery. The strength of stimulating current for direct stimulation was varied from 10 to 30 mA. Postoperatively, the motor function was evaluated by using a 5-score scale, and the data were compared to the preoperative data.
RESULTS
According to preoperative DTI tractography in patients with grade I-II gliomas, the corticospinal tracts were infiltrated in 2 cases, displaced in 3 cases, and intact in 5 cases. In patients with grade III-IV gliomas and metastases, the tracts were infiltrated in 8 cases, displaced in 4 cases, and intact in 7 cases. Motor responses evoked by direct electrical stimulation were obtained in 5 out of 6 patients with the pyramidal tract displaced by the tumor and in 7 out of 8 patients with the tract infiltrated by the tumor. In the case of the intact tract, the PT to tumor distance and the stimulus strength play an important role: responses were obtained in 4 out of 10 patients. In the case of transcranial motor evoked potentials (TCMEPs), no dynamics of the potential amplitude was detected in 17 out of 26 patients during surgery; a reduced TCMEP amplitude was detected in 9 patients.
CONCLUSION
1. Patients with an infiltrated or displaced pyramidal tract had significantly more often hemiparesis before surgery and aggravation of hemiparesis after the surgery compared to patients with an intact tract. 2. In the case of direct electrical stimulation of the PT, motor responses (according to preoperative DTI tractography) were significantly more often observed for the pyramidal tract infiltrated and displaced by the tumor. 3. A reduction in the motor neurologic deficit in the postoperative period was significantly more often observed for application of a larger current strength during direct electrical stimulation. 4. Persistence of the TCMEP amplitude during surgery is a reliable predictor for no aggravation of the motor neurological deficit after surgery. Postoperative aggravation of hemiparesis was significantly more often observed when TC MEPs decreased during surgery.
Topics: Adult; Brain Neoplasms; Diffusion Tensor Imaging; Female; Humans; Male; Middle Aged; Monitoring, Intraoperative; Pyramidal Tracts
PubMed: 27029327
DOI: 10.17116/neiro20168015-18 -
Compensatory contribution of the contralateral pyramidal tract after experimental cerebral ischemia.Frontiers of Neurology and Neuroscience 2013Many people escape sudden death from ischemic brain stroke, but suffer from severe disabilities such as aphasia and/or paralysis. These survivors of focal brain injury... (Review)
Review
Many people escape sudden death from ischemic brain stroke, but suffer from severe disabilities such as aphasia and/or paralysis. These survivors of focal brain injury need chronic care to recover from and/or compensate for the impaired sensory and motor functions previously controlled by the focal ischemic core. Functional compensation not only involves the remaining brain areas around the infarction but also the areas contralateral to the stroke lesion, with the need for remodeling of neuronal circuits in some cases. In this review, recent human and animal studies are presented to aid in the understanding of such plasticity in areas contralateral to the stroke lesion providing a new model for rehabilitation. It is well known in the medical field that the intact contralateral hemisphere is recruited for functional remodeling of modalities such as speech. However, the detailed mechanisms underlying these phenomena are less clear. In rodents, in vivo imaging techniques combined with other traditional techniques such as electrophysiology and behavior have revealed that functional recovery is achieved by specific synaptic (neuronal circuit) remodeling of the contralateral area in the 1st week after a focal stroke. The intact contralateral hemisphere can therefore potentially adopt a bilateral function, even in adults, following proper remodeling of neuronal circuits. These recent results suggest a possible new pathway using the intact hemisphere's function to recover lost functions stroke patients.
Topics: Adaptation, Physiological; Animals; Brain; Brain Ischemia; Humans; Neuronal Plasticity; Pyramidal Tracts
PubMed: 23859961
DOI: 10.1159/000346409